MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'European Journal of Medical Genetics' source. Fri, 19 Mar 2010 17:00:51 +0100 http://www.medworm.com/index.php?rid=3351493&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20215058%26dopt%3DAbstract We describe a case of a female infant with a de novo deletion. Dysmorphic features and congenital heart disease led to a clinical genetics assessment on day 1 of life. Chromosomal analysis showed an interstitial deletion with a female karyotype 46,XX, del (3)(q23q25.1)dn. Subsequent array CGH demonstrated the breakpoints as 3q22.3q25.1. This is the first documented association with a truncus arteriosus. We identify an emerging clinical phenotype of microphthalmia, microcephaly, congenital heart disease, slow feeding, skeletal abnormalities, with an abnormal facies and developmental delay. Array CGH demonstrated that the FOXL2 gene responsible for BPES was not deleted in this patient. PMID: 20215058 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3351493 Thu, 04 Mar 2010 00:00:00 +0100 3351493 http://www.medworm.com/index.php?rid=3335807&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197130%26dopt%3DAbstract Authors: Hannes F, Drozniewska M, Vermeesch JR, Haus O Wolf-Hirschhorn Syndrome (WHS) is caused by deletions on chromosome 4p and is clinically well defined. Genotype-phenotype correlations of patients with WHS point to a critical locus to be responsible for the main characteristics of this disorder. Submicroscopic duplications of this region, however, are not known. Here we report a patient with an interstitial 560kb duplication overlapping this critical locus. The present case shows that not only deletions but also duplications of the Wolf-Hirshhorn critical region cause mental retardation and multiple congenital anomalies. Interestingly, the duplication phenotype overlaps partially with the deletion phenotype. However, his facial phenotype differs from the typical WHS gestalt. P... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3335807 Sat, 27 Feb 2010 00:00:00 +0100 3335807 http://www.medworm.com/index.php?rid=3276425&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20152949%26dopt%3DAbstract Authors: Elalaoui SC, Jaouad IC, Rifai L, Sefiani A Microtia (MIM600674) is a congenital malformation which occurs in 1/8000-10000 births. It is characterized by a small, and abnormally shaped pinna. It ranges in severity from a bump of tissue to a partially formed ear cup. Microtia is often associated with atresia of the external auditory canal. Familial microtia with meatal atresia has been reported, either with dominant or recessive inheritance, which makes genetic counselling difficult in sporadic cases. In the present paper, we report the case of a family with congenital microtia and conductive deafness in two generations, suggesting autosomal dominant inheritance with variable expression and incomplete penetrance. PMID: 20152949 [PubMed - as supplied by publisher] (Source: Eu... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3276425 Tue, 09 Feb 2010 00:00:00 +0100 3276425 http://www.medworm.com/index.php?rid=3276424&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20152950%26dopt%3DAbstract Authors: Möhrenschlager M, Lauenstein M, Ring J, Steiner C PMID: 20152950 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3276424 Tue, 09 Feb 2010 00:00:00 +0100 3276424 http://www.medworm.com/index.php?rid=3248745&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20132917%26dopt%3DAbstract We report a patient presenting with oculoauriculovertebral spectrum and a de novo balanced reciprocal translocation t(9;18) (p23;q12.2). Physical mapping of the translocation breakpoints by fluorescent in situ hybridization showed that the breakpoints are located in two regions encompassing gene deserts. An additional paternally inherited duplication in 18p11.23p11.31 was identified by array-CGH. We discuss the possible involvement of these chromosomal abnormalities in OAVS. PMID: 20132917 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3248745 Mon, 01 Feb 2010 00:00:00 +0100 3248745 http://www.medworm.com/index.php?rid=3248744&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20132918%26dopt%3DAbstract We present a detailed comparison of the breakpoints, inheritance, X-inactivation and clinical phenotype in our cohort and a review of the literature for a total of 41 patients. To date, this report is the largest compilation of clinical and array data regarding the microduplication of Xp22.31 and will serve to broaden the knowledge of regions involving copy number variation (CNV). PMID: 20132918 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3248744 Mon, 01 Feb 2010 00:00:00 +0100 3248744 http://www.medworm.com/index.php?rid=3209382&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20096387%26dopt%3DAbstract We report on a 7-year-old girl with severe mental retardation (MR), autism, micro-brachycephaly, generalized muscle hypotonia with distal hypotrophy of lower limbs, scoliosis and facial dysmorphisms. Array-CGH analysis identified a 1.1 Mb deletion of chromosome Xq22.1. Further analysis demonstrated that the deletion was inherited from her mother who showed mild MR, short stature, brachycephaly, epilepsy and a Borderline Personality Disorder. Microsatellite segregation analysis revealed that the rearrangement arose de novo in the mother on the paternal X chromosome. The deleted Xq22.1 region contains part of the NXF gene cluster which is involved in mRNA nuclear export and metabolism. Among them, the NXF5 gene has already been linked to mental retardation whereas NXF2 protein has been recen... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3209382 Tue, 19 Jan 2010 00:00:00 +0100 3209382 http://www.medworm.com/index.php?rid=3186069&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20080219%26dopt%3DAbstract We report three sibs with a syndrome consisting of severe mental retardation, considerably elevated serum levels of alkaline phosphatase, hypoplastic terminal phalanges, and distinct facial features. Clinically and radiologically, shortness of distal phalanges could be demonstrated in all of them. Their particular facial appearance led us to two earlier reported familial cases with convincing clinical similarities. We suggest a specific clinical entity within the spectrum of patients with mental retardation and hyperphosphatasia which is in particular characterized by a recognizable facial gestalt and brachytelephalangy. PMID: 20080219 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3186069 Thu, 14 Jan 2010 00:00:00 +0100 3186069 http://www.medworm.com/index.php?rid=3180565&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20074678%26dopt%3DAbstract In this report, we describe a child with speech delay and features of an autistic spectrum disorder and with a 1.6 Mb deletion of 8q22.1. The deletion has significant chromosomal overlap with previously reported examples of NMLFS, but our patient lacks the clinical features noted in the published cases. PMID: 20074678 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3180565 Mon, 11 Jan 2010 00:00:00 +0100 3180565 http://www.medworm.com/index.php?rid=3161284&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20060941%26dopt%3DAbstract Authors: Draaken M, Reutter H, Schramm C, Bartels E, Boemers TM, Ebert AK, Rösch W, Schröder A, Stein R, Moebus S, Stienen D, Hoffmann P, Nöthen MM, Ludwig M The exstrophy-epispadias complex (EEC) comprises a spectrum of urogenital anomalies in which part or all of the distal urinary tract fails to close. The present study aimed to identify microaberrations characterized by loss or gain of genomic material that contribute to the EEC at a genome-wide level. Molecular karyotyping, utilizing 549,839 single nucleotide polymorphisms (SNPs) with an average spacing of 5.7 kilobases, was performed to screen an initial cohort of 16 patients with non-syndromic EEC. A de novo microduplication involving chromosomal region 22q11.21 was identified in one patient with classic exstrophy... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3161284 Thu, 07 Jan 2010 00:00:00 +0100 3161284 http://www.medworm.com/index.php?rid=3146539&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20045092%26dopt%3DAbstract We report the first case of agalsidase beta treatment throughout pregnancy. High-range proteinuria remained stable and the patient gave birth to a healthy boy after an uncomplicated pregnancy. The decision to administer ERT during pregnancy should be made on an individual basis, considering the FD status and possible risks. PMID: 20045092 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3146539 Thu, 31 Dec 2009 00:00:00 +0100 3146539 http://www.medworm.com/index.php?rid=3146538&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20045748%26dopt%3DAbstract Authors: Lundin J, Söderhäll C, Lundén L, Hammarsjö A, White I, Schoumans J, Kockum CC, Läckgren G, Nordenskjöld A Bladder exstrophy is a congenital malformation of the bladder and urethra. The genetic basis of this malformation is unknown however it is well known that chromosomal aberrations can lead to defects in organ development. A few bladder exstrophy patients have been described to carry chromosomal aberrations. Chromosomal rearrangements of 22q11.2 are implicated in several genomic disorders i.e. DiGeorge/velocardiofacial- and cat-eye syndrome. Deletions within this chromosomal region are relatively common while duplications of 22q11.2 are much less frequently observed. An increasing number of reports of microduplications of this region describe a ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3146538 Thu, 31 Dec 2009 00:00:00 +0100 3146538 http://www.medworm.com/index.php?rid=3136968&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20044043%26dopt%3DAbstract We report a 7 year-old boy with a clinical, radiological and molecular diagnosis (mutation c.436G>C (p.G146R) in CSTK) of pycnodysostosis, who developed intracranial hypertension that required surgical decompression. Despite patent fontanels, the cause of the intracranial hypertension was surprisingly identified to be a combination of coronal and metopic craniostenosis. Intracranial hypertension and craniostenosis have only been reported once in pycnodysostosis, which is on the contrary characterized by delayed suture closure and persistent open fontanels. Our observation confirms that, indeed, it represents a rare but life-threatening complication of pycnodysostosis. We strongly suggest including systematic examination of fundus oculi and monitoring of OFC in the systematic clinical fo... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3136968 Mon, 28 Dec 2009 00:00:00 +0100 3136968 http://www.medworm.com/index.php?rid=3102503&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20004752%26dopt%3DAbstract CONCLUSIONS: Our results suggest that the common submicroscopic "genomic disorders" (microdeletion and microduplication syndromes) would not be frequently detected in the first trimester anomalies screening. PMID: 20004752 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3102503 Mon, 14 Dec 2009 00:00:00 +0100 3102503 http://www.medworm.com/index.php?rid=3102502&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20004753%26dopt%3DAbstract Authors: Schönherr N, Spengler S, Binder G, Eggermann T Silver-Russell syndrome (SRS) is a sporadic and heterogeneous disease that is mainly associated with intrauterine and postnatal growth retardation. The most frequent known aberration in SRS patients is a hypomethylation of the imprinting control region 1 (ICR1) in 11p15 ( approximately 38%). Up to now the basic mechanisms leading to this imprinting defect are unknown. Based on the recent findings that a reduced level of the methyl-CpG binding protein 3 (Mbd3) in mice results in a specific hypomethylation of the ICR1 and in a smaller size of embryos we hypothesized that mutations in the genomic sequence of the human MBD3 gene might cause SRS. We carried out mutation analysis of MBD3 in 20 SRS patients with hypomethylation of t... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3102502 Fri, 11 Dec 2009 00:00:00 +0100 3102502 http://www.medworm.com/index.php?rid=3036251&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19941982%26dopt%3DAbstract Authors: Villamizar C, Regalado ES, Fadulu VT, Hasham SN, Gupta P, Willing MC, Kuang SQ, Guo D, Muilenburg A, Yee RW, Fan Y, Towbin J, Coselli JS, Lemaire SA, Milewicz DM Marfan syndrome (MFS) is an autosomal dominant condition with pleiotropic manifestations involving the skeletal, ocular, and cardiovascular systems. The diagnosis is based primarily on clinical involvement of these and other systems, referred to as the Ghent criteria. We have identified three Hispanic families from Mexico with cardiovascular and ocular manifestations due to novel FBN1 mutations but with paucity of skeletal features. The largest family, hMFS001, had a frameshift mutation in exon 24 (3075delC) identified as the cause of aortic disease in the family. Assessment of eight affected adults revealed no major ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3036251 Mon, 23 Nov 2009 00:00:00 +0100 3036251 http://www.medworm.com/index.php?rid=3036250&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19941983%26dopt%3DAbstract Authors: van der Zwaag PA, Dijkhuizen T, Gerssen-Schoorl KB, Colijn AW, Broens PM, Flapper BC, van Ravenswaaij-Arts CM Postaxial polydactyly type A2 (PAP-A2; OMIM 602085) is a common feature seen in patients with a partial duplication of the long arm of chromosome 13. Dose dependency has been shown for digital malformations in this region, deletions resulting in oligodactyly and duplications in polydactyly. We aimed to narrow down the critical region for PAP-A2 in order to identify candidate genes. We performed chromosomal analysis, FISH and array-CGH in a patient with an interstitial duplication of chromosome 13(q31.3q32.1) and a mild phenotype including postaxial polydactyly. The duplicated region spanned 5.59 Mb (89.67-95.25 Mb) and contained eleven known genes, including GPC5 and G... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3036250 Mon, 23 Nov 2009 00:00:00 +0100 3036250 http://www.medworm.com/index.php?rid=3030860&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19932204%26dopt%3DAbstract We report five cases in two unrelated families (one sporadic case in the first family and three siblings and their father in the second family) with the same association of polyvalvular heart disease, distinctive facial appearance, and, except the father in family 2, major joint hypermobility. Interestingly, in three of our patients (2 siblings and the sporadic case), electron microscopy revealed characteristic ultrastructural skin abnormalities with abnormal amorphous or microfibrillar deposits under the capillary basal membrane in the papillary dermis, suggestive of a connective tissue disorder, but different from Marfan syndrome or Ehlers-Danlos syndrome. Moreover, in family 2, three others sibs died in early infancy of their heart defect. Our two families and the other published cases ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3030860 Thu, 19 Nov 2009 00:00:00 +0100 3030860 http://www.medworm.com/index.php?rid=2967893&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19887127%26dopt%3DAbstract We report on a newborn from consanguineous parents who presented with multiple congenital anomalies and neonatal hemochromatosis. The syndrome consisted of intrauterine growth retardation, intestinal atresia, gallbladder aplasia and diabetes mellitus, and fitted with the diagnosis of Martinez-Frias syndrome, a very rare autosomal recessive phenotype, the gene of which remains to be identified. We suggest that neonatal hemochromatosis may be part of the Martinez-Frias syndrome. Molecular analyses in this and other reported patients with the Martinez-Frias syndrome should shed light on gut development and iron metabolism. PMID: 19887127 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2967893 Sat, 31 Oct 2009 00:00:00 +0100 2967893 http://www.medworm.com/index.php?rid=2959544&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879983%26dopt%3DAbstract Authors: Voermans NC, Hosman A, van Alfen N, Bartels RH, de Kleuver M, Op den Akker JW, van Engelen BG Marfan syndrome is a heritable connective tissue disorder due to mutations in fibrillin-1. It presents with cardiovascular, ocular, skeletal, pulmonary and dural signs and symptoms. Some of the symptoms of later onset are those associated with scoliosis and dural ectasia. This is the enlargement of the neural canal especially in the lower lumbar and sacral region and occurs in over 90% of Marfan patients. We here report three patients with lumbar and/or sacral radiculopathy due to (kypho)scoliosis and dural ectasia with spinal meningeal cysts. The pain, muscle weakness, muscle atrophy, and sensory disturbances illustrate the severe neurological complications which may occur in Marfan ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2959544 Thu, 29 Oct 2009 00:00:00 +0100 2959544 http://www.medworm.com/index.php?rid=2959547&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878741%26dopt%3DAbstract Authors: Van Dijk FS, Pals G, Van Rijn RR, Nikkels PG, Cobben JM In 1979 Sillence proposed a classification of Osteogenesis Imperfecta (OI) in OI types I, II, III and IV. In 2004 and 2007 this classification was expanded with OI types V-VIII because of distinct clinical features and/or different causative gene mutations. We propose a revised classification of OI with exclusion of OI type VII and VIII since these types have been added because of genetic criteria (autosomal recessive inheritance) while the clinical and radiological features are indistinguishable from OI types II-IV. Instead, we propose continued use of the Sillence criteria I, II-A, II-B, II-C, III and IV for clinical and radiological classification of OI with additional mentioning of the causative mutated gene to this c... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2959547 Tue, 27 Oct 2009 00:00:00 +0100 2959547 http://www.medworm.com/index.php?rid=2959546&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878742%26dopt%3DAbstract Authors: Gerkes EH, van der Kevie-Kersemaekers AM, Yakin M, Smeets DF, van Ravenswaaij-Arts CM Roberts syndrome/SC phocomelia is a rare, autosomal recessive syndrome characterised by pre- and postnatal growth retardation, microcephaly, craniofacial anomalies, mental retardation, and tetraphocomelia in varying degrees of severity. The clinical diagnosis can be challenging in phenotypically mild cases. In the extremely mild case presented here, specific mitotic abnormalities were detected and proved to be very helpful, since Roberts syndrome/SC phocomelia could be diagnosed after finding premature centromere separation and somatic aneuploidy at routine karyotyping. We discuss these and other mitotic cytogenetic abnormalities that can be of significant diagnostic importance, but which wil... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2959546 Tue, 27 Oct 2009 00:00:00 +0100 2959546 http://www.medworm.com/index.php?rid=2959545&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878743%26dopt%3DAbstract In this study, genomic DNAs from 132 French patients with unexplained mental retardation were analysed by genomewide high-resolution Agilent((R)) 44K oligonucleotide arrays. The results were in accordance with those observed in previous studies: the detection rate of pathogenic CNVs was 14.4%. A non-random involvement of several chromosomal regions was observed. Some of the microimbalances recurrently involved regions (1q21.1, 2q23.1, 2q32q33, 7p13, 17p13.3, 17p11.2, 17q21.31) corresponding to known or novel syndromes. For all the pathogenic CNVs, further cases are needed to allow more accurate genotype-phenotype correlations underscoring the importance of databases to group patients with similar molecular data. PMID: 19878743 [PubMed - as supplied by publisher] (Source: European Journ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2959545 Tue, 27 Oct 2009 00:00:00 +0100 2959545 http://www.medworm.com/index.php?rid=2934409&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19857611%26dopt%3DAbstract Authors: Wincent J, Schoumans J, Anderlid BM Many distal deletions of chromosome 11q have been described, but reports on deletion of 11q13-q14 are rare in the literature. Here we describe the genotype and phenotype of a boy with a deletion of this region. We fine mapped the aberration with array-CGH, revealing an 18.2 Mb deletion. The main clinical features included microcephaly, ptosis and moderate developmental delay. The symptoms partially overlap with previously reported patients with a deletion in the same region. PMID: 19857611 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2934409 Fri, 23 Oct 2009 00:00:00 +0100 2934409 http://www.medworm.com/index.php?rid=2894916&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19822228%26dopt%3DAbstract This article reviews these new data alongside other genetic causes of syndromic esophageal atresia, and also highlights information from relevant mouse models, particularly those for genes in the Sonic Hedgehog pathway. PMID: 19822228 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2894916 Thu, 08 Oct 2009 23:00:00 +0100 2894916 http://www.medworm.com/index.php?rid=2876906&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19808103%26dopt%3DAbstract We report here four patient from three families with GJA1 mutations, one of them diagnosed prenatally. The three mutations (c.52T > C/p.Ser18Pro, c.689_690delTA/p.Tyr230CysfsX6, c.442C > G/p.Arg148Gly) have been reported once before. Two patient had white matter hypersignal anomalies, associated in one case with mental retardation, but asymptomatic in the other one, an observation that leas us to discuss systematic neuroradiological imaging for ODDD. One case has optic atrophy, another has hypospadias. The patient carrying a truncating mutation of Cx43 did not have palmoplantar keratoderma, in contradiction with the previously suggested genotype-phenotype correlation between truncating mutation and skin involvement. PMID: 19808103 [PubMed - as supplied by publisher] (Source: Euro... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2876906 Sun, 04 Oct 2009 23:00:00 +0100 2876906 http://www.medworm.com/index.php?rid=2869797&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19800039%26dopt%3DAbstract We report on a 6-year-old male child displaying an association of congenital diaphragmatic hernia (CDH), lung hypoplasia, corneal clouding and coarse face in the absence of distal digital/nail hypoplasia. Based on the recently published diagnostic guidelines, our patient fits the narrow definition of FS. Only a minority of FS patients surviving the neonatal period have been reported, thus limiting the recognition of the infantile phenotype. We compared the features observed in our proband with those of 10 published survivors. Neurological impairment ranging from mild to severe was present in all patients, while seizures manifested in one third of them, often in association with central nervous system malformations. Other characteristic features included central-paracentral corneal clouding... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2869797 Tue, 29 Sep 2009 23:00:00 +0100 2869797 http://www.medworm.com/index.php?rid=2828839&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19772933%26dopt%3DAbstract Authors: Reddy S, Dolzhanskaya N, Krogh J, Velinov M A 2.5 years old girl presented with moderate mental retardation, microcephaly, arching eyebrows, low set ears, long eyelashes, persistent fetal pads and clinodactyly. About 1 Mb deletion in the chromosomal region 1q21.3 was identified using BAC array CGH analysis. The parental follow up FISH analysis was normal. Further study of the deletion using a 244K oligo-array of Agilent Technologies Inc., Santa Clara, CA, USA. defined the deleted region to span about 1.4 Mb with approximate genomic location chr1:152,511,593-153,993,103 (NCBI genome build 36). This is a novel deletion, not reported to-date. Larger proximal 1q deletions that were previously reported typically included microcephaly, mental retardation and multiple congenital anom... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2828839 Fri, 18 Sep 2009 23:00:00 +0100 2828839 http://www.medworm.com/index.php?rid=2828838&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19772934%26dopt%3DAbstract Authors: Yeung A, Bruno D, Scheffer IE, Carranza D, Burgess T, Slater HR, Amor DJ Microdeletions at 14q12 that include FOXG1, or loss of function mutations in FOXG1, are associated with the congenital variant of Rett syndrome. By SNP microarray analysis we identified a corresponding microduplication at 14q12 in a nine year old girl with symptomatic generalized epilepsy, severe intellectual impairment, and minor dysmorphisms, but without microcephaly. The 14q12 microduplication comprised 4.45 Mb of DNA and included FOXG1. This is the first report of duplication involving FOXG1 and suggests a dosage sensitive role for FOXG1 in brain development. PMID: 19772934 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2828838 Fri, 18 Sep 2009 23:00:00 +0100 2828838 http://www.medworm.com/index.php?rid=2821100&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19770079%26dopt%3DAbstract In this study, a familial occurrence of the 16p11.2 deletion was identified in association with hemivertebrae The proband was a 3-year-old boy who showed developmental delay, displayed hyperactive but not autistic behavior, and had hemivertebrae, rib anomalies, and inguinal hernia. Familial investigation revealed that his mother shared the same deletion. Under the hypothesis of the existence of an unmasked mutation in the deletion region, we analyzed the sequence of the T-box 6 gene (TBX6) included in the deletion region, but did not detect any mutation. This suggests that haploinsufficiency of TBX6 can lead to vertebral malformation in low penetrance. PMID: 19770079 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2821100 Thu, 17 Sep 2009 23:00:00 +0100 2821100 http://www.medworm.com/index.php?rid=2821101&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19765681%26dopt%3DAbstract Authors: Buysse K, Chiaie BD, Van Coster R, Loeys B, De Paepe A, Mortier G, Speleman F, Menten B Molecular karyotyping has moved from bench to bedside for the genetic screening of patients with mental retardation and/or congenital anomalies. The commercial availability of high-resolution microarray platforms has significantly facilitated this process. However, the notion that copy number variants are also abundantly present in the general population challenges the interpretation of the clinical significance of detected copy number variants (CNVs) in these patients. Moreover, the awareness of incomplete penetrance and variable expression, exemplified by the inheritance of causal CNVs from apparently unaffected parents, has further blurred the boundary between benign and pathogenic varia... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2821101 Mon, 14 Sep 2009 23:00:00 +0100 2821101 http://www.medworm.com/index.php?rid=2779451&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19737635%26dopt%3DAbstract This report adds another rare, but serious manifestation to the multiorgan involvement found in TBS. PMID: 19737635 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2779451 Fri, 04 Sep 2009 23:00:00 +0100 2779451 http://www.medworm.com/index.php?rid=2779452&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19735747%26dopt%3DAbstract We report on two families in which the parental origin of duplications of the BWS imprinted regions on chromosome 11p15 influences the phenotype. In family A the transmission of a t(4;11)(q35;p15.5) translocation results in duplication of BWSIC1 and BWSIC2. If this duplication is transmitted from the father, the extra chromosomal material has the paternal imprint. This results in overexpression of IGF2 and consequently an overgrowth phenotype. If the duplication is transmitted from the mother, the extra chromosomal material has the maternal imprint, resulting in overexpression of CDKN1C and a growth retardation phenotype. In family B an interstitial duplication of BWSIC1 results in an overgrowth phenotype when inherited from the father, similar to family A. However, no change in phenotype ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2779452 Thu, 03 Sep 2009 23:00:00 +0100 2779452 http://www.medworm.com/index.php?rid=2774364&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19733267%26dopt%3DAbstract We describe a patient presenting with developmental delay, patent foramen ovale, moderate short QT interval, and facial dysmorphism including left microtia, preauricular tag and pit, wide left corner of the mouth, and left hemifacial microsomia, fitting with the oculoauriculovertebral spectrum. We identified a de novo 2.3 Mb deletion in the 12p13.33 region that contains eighteen genes. Amongst those, the WNT5B gene stands out as a possible candidate. However, we did not find any mutation of this gene neither in our patient nor in a series of 53 OAVS patients. The CACNA1C gene is interrupted by the centromeric breakpoint of the deletion and its inactivation probably accounts for the short QT interval of the patient. We speculate that the phenotype of our patient may be explained by the comb... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2774364 Tue, 01 Sep 2009 23:00:00 +0100 2774364 http://www.medworm.com/index.php?rid=2758641&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19716450%26dopt%3DAbstract We report on three monozygotic female twins who are discordant for a VM-DG syndrome resembling KTS. We suggest that our observation is consistent with the concept of polygenic paradominant inheritance involving two or more genes. We discuss the published observations in twins discordant for other disorders associated with disturbed growth regulation such as Beckwith-Wiedemann syndrome and Silver-Russell syndrome, and the occurrence in cousins with KTS and Beckwith-Wiedemann syndrome, which are best explained by an imprinting disturbance. We propose that, similarly, disturbed imprinting plays a role in the pathogenesis of VM-DG syndromes in general, and suggest the same may hold for KTS in sensu strictu or Proteus syndrome. Further studies to investigate imprinting status in VM-DG syndromes... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2758641 Wed, 26 Aug 2009 23:00:00 +0100 2758641 http://www.medworm.com/index.php?rid=2741784&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19706342%26dopt%3DAbstract We describe a Finnish boy with megalocornea, urticaria pigmentosa, mild delay in speech and motor development, and slightly dysmorphic facial features. The karyotype and the array-CGH analysis did not reveal any abnormalities. This combination of symptoms has not been reported previously suggesting this might be a new syndrome with an unknown etiology. PMID: 19706342 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2741784 Fri, 21 Aug 2009 23:00:00 +0100 2741784 http://www.medworm.com/index.php?rid=2702751&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19679203%26dopt%3DAbstract Authors: Shaw AC, Hennekam RC Genetic medicine is said to be entering another era. Recent technological developments such as high resolution array techniques and next-generation sequencing have dramatically increased the power of genetic testing. However, the function of the majority of genes remains unknown. The complex interactions underpinning gene expression in humans can be studied only in part by laboratory and animal studies, and will only be possible by studies in humans. Consequently, observational studies which systematically record human phenotype data are urgently needed to interpret molecular genetic variation. PMID: 19679203 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2702751 Sun, 09 Aug 2009 23:00:00 +0100 2702751 http://www.medworm.com/index.php?rid=2696353&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19665063%26dopt%3DAbstract Authors: Fauth C, Kehrer-Sawatzki H, Zatkova A, Machherndl-Spandl S, Messiaen L, Amann G, Hainfellner JA, Wimmer K We analyzed two unrelated male patients in whom neurofibromatosis type 1 (NF1) was not suspected until they presented with malignant peripheral nerve sheath tumours (MPNSTs) in their thirties and forties, respectively. Patient A presented with progressive peroneus paresis due to a rapidly growing MPNST in the thigh. MRI examination revealed multiple symmetrical spinal neurofibromas in this patient as well as in patient B who presented at the age of 42 with paraparesis and an MPNST at spinal level L4. Dermal features in both patients were strikingly mild, therefore both patients were considered belonging to the NF1-subform of spinal neurofibromatosis (SNF). The novel NF1 mu... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2696353 Wed, 05 Aug 2009 23:00:00 +0100 2696353 http://www.medworm.com/index.php?rid=2650363&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19632364%26dopt%3DAbstract CONCLUSION: These findings suggest the existence of familial as opposed to the sporadic ESCC. By the theory of "two-hit" origin of cancer, these findings also suggest that the "first hit", a genetic predisposition, is inherited in familial ESCC. PMID: 19632364 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2650363 Fri, 24 Jul 2009 23:00:00 +0100 2650363 http://www.medworm.com/index.php?rid=2650360&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19635601%26dopt%3DAbstract Authors: Bessières-Grattagliano B, Foliguet B, Devisme L, Loeuillet L, Marcorelles P, Bonnière M, Laquerrière A, Fallet-Bianco C, Martinovic J, Zrelli S, Leticee N, Cayrol V, Etchevers HC, Vekemans M, Attie-Bitach T, Encha-Razavi F Cerebral proliferative glomeruloid vasculopathy (PGV) is a severe disorder of brain angiogenesis, resulting in abnormally thickened and aberrant perforating vessels, forming glomeruloids with inclusion-bearing endothelial cells. This peculiar vascular malformation was delineated by Fowler in 1972 as a stereotyped lethal fetal phenotype associating hydranencephaly-hydrocephaly with limb deformities, called Fowler syndrome (FS) or "proliferative vasculopathy and hydranencephaly-hydrocephaly" or "encephaloclastic proliferative vasculopathy" (OMIM... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2650360 Thu, 23 Jul 2009 23:00:00 +0100 2650360 http://www.medworm.com/index.php?rid=2650362&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19632365%26dopt%3DAbstract In conclusion, this study does not provide evidence that ZFP57 mutations are the cause of 11p15-hypomethylation in SRS patients and contribute to the aetiology of SRS. PMID: 19632365 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2650362 Wed, 22 Jul 2009 23:00:00 +0100 2650362 http://www.medworm.com/index.php?rid=2650361&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19632366%26dopt%3DAbstract Authors: De Sario A Epigenetics is the study of heritable changes in gene expression that occur without a change in the DNA sequence. Most constitutional defects in genes encoding components of the machinery that regulates the epigenome lead to embryonic death. Hypomorphic mutations may be compatible with life, but lead to severe developmental disorders. Their study is of great importance to our understanding of epigenetics and may clarify the interplay between different epigenetic mechanisms. This review will briefly introduce DNA methylation, post-translational histone modifications, and non-coding small RNA transcription, which are the best known epigenetic mechanisms. Then it will describe five human disorders (RETT, ATRX, ICF, Coffin-Lowry, and Rubinstein-Taybi) resulting from mut... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2650361 Wed, 22 Jul 2009 23:00:00 +0100 2650361 http://www.medworm.com/index.php?rid=2607066&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19595804%26dopt%3DAbstract We report two siblings with FHLH caused by a PRF1 mutation. The first child died in utero with hydrops fetalis and the second presented soon after birth with fatal multiple organ failure. Post-mortem DNA analysis showed a homozygous c.666C>A (p.His222Gln) mutation in the PRF1 gene in both cases, with their non-consanguineous parents being heterozygous for the same mutation. Review of the literature shows that perinatal presentation of FHLH is rare. Diagnosis is difficult because in most cases histiologic examination reveals no hemophagocytosis and the disease is rapidly fatal. The association between hydrops fetalis and FHLH has been reported in four previous reports. We present the first case of hydrops fetalis caused by FHLH, confirmed by DNA analysis. FHLH should be included in the d... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2607066 Wed, 08 Jul 2009 23:00:00 +0100 2607066 http://www.medworm.com/index.php?rid=2607065&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19596467%26dopt%3DAbstract Authors: Claudia F, Fernando K, Pablo N, Chong K, Débora B, Lílian A, Koiffmann Célia P Sotos syndrome (MIM #117550) is an autosomal dominant condition characterized by pre and postnatal overgrowth, macrocephaly and typical facial gestalt with frontal bossing, hypertelorism, antimongoloid slant of the palpebral fissures, prominent jaw and high and narrow palate. This syndrome is also frequently associated with brain, cardiovascular, and urinary anomalies and is occasionally accompanied by malignant lesions such as Wilms tumor and hepatocarcinoma. The syndrome is known to be caused by mutations or deletions of the NSD1 gene. To detect both 5q35 microdeletions and partial NSD1 gene deletions we screened 30 Brazilian patients with clinical diagnosis of Sotos syndrome by mul... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2607065 Tue, 07 Jul 2009 23:00:00 +0100 2607065 http://www.medworm.com/index.php?rid=2577467&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19577669%26dopt%3DAbstract Authors: Stora S, Conte M, Chouery E, Richa S, Jalkh N, Gillart AC, de Joannis AL, Mégarbané A The facio-oculo-acoustico-renal syndrome (FOAR) is a rare autosomal recessive syndrome characterized by the presence of dysmorphic facial features, ocular anomalies, sensorineural hearing loss, and proteinuria. Diaphragmatic hernia, exomphalos, absent or abnormal corpus callosum, and myopia, can also be part of the syndrome. The disorder is caused by mutations of the LRP2 gene located on chromosome 2q23.3-q31.1. We hereby report the case of a 56-year-old female patient with typical FOAR features. Molecular study of the LRP2 gene revealed the presence of a novel splice-site mutation. In addition to what was reported in FOAR syndrome, this patient had a megadolichocolon complicated by... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2577467 Wed, 01 Jul 2009 23:00:00 +0100 2577467 http://www.medworm.com/index.php?rid=2577466&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19577670%26dopt%3DAbstract We describe a patient homozygous for a novel mutation in COG7, coding for one of the subunits of the Conserved Oligomeric Golgi complex, involved in retrograde vesicular trafficking. His brother showed a similar clinical syndrome and glycosylation defect but no DNA could be obtained from this patient. This mutation, c.170-7A>G, activates a cryptic splice acceptor and leads to the insertion of 2 amino acids at protein level (p.56-57insAT). The insertion disturbs the structure and function of the Conserved Oligomeric Golgi complex. In comparison to the previously described patients with a different COG7 mutation, intrauterine growth retardation and dysmorphic features were absent and there was a longer survival. PMID: 19577670 [PubMed - as supplied by publisher] (Source: European Jour... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2577466 Wed, 01 Jul 2009 23:00:00 +0100 2577466 http://www.medworm.com/index.php?rid=2577470&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19576302%26dopt%3DAbstract We report a 4.5Mb deletion of 2q33.1 in an individual with developmental delay and cleft palate. There have been various previous reports of deletions of 2q3, all with varying breakpoints and all larger than the current case. Whilst there is some variation in the phenotypes of patients with 2q3 deletions all share a commonly deleted region within 2q33.1 which includes SATB2, a gene previously shown to be associated with cleft palate. The phenotypic features of our patient are milder than those reported so far. PMID: 19576302 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2577470 Mon, 29 Jun 2009 23:00:00 +0100 2577470 http://www.medworm.com/index.php?rid=2577469&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19576303%26dopt%3DAbstract We report on a patient carrying a de novo interstitial deletion of chromosomal region 6q23.2-24.1. Interstitial deletions of 6q are rarely reported in the literature. Indeed, only four patients with interstitial deletions overlapping partially with the deleted region in our patient are described in the literature. The aberration was detected by GTG-banding. The size of the deletion was further refined by array-CGH and subsequently fine mapped by quantitative real-time PCR. The exact size of the deletion and the sequence composition of the breakpoints were determined by breakpoint spanning PCR and subsequent sequencing. The patient presented with microcephaly, short stature, patent ductus arteriosus, sensorineural hearing loss, mental retardation, reduced speech development, and abnormal be... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2577469 Mon, 29 Jun 2009 23:00:00 +0100 2577469 http://www.medworm.com/index.php?rid=2577468&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19576304%26dopt%3DAbstract Authors: Bremer A, Schoumans J, Nordenskjöld M, Anderlid BM, Giacobini M Seven cases with an interstitial deletion of the short arm of chromosome 6 involving the 6p22 region have previously been reported. The clinical phenotype of these cases includes developmental delay, brain-, heart- and kidney defects, eye abnormalities, short neck, craniofacial, malformations, hypotonia, as well as clinodactyly or syndactyly. We here report a patient with a 7.1 Mb interstitial deletion of chromosome band 6p22.3, detected by genome-wide screening array CGH. The patient is a four-year-old girl with developmental delay and dysmorphic features including eye abnormalities, short neck and a ventricular septum defect. The deleted region at 6p22.3 in our patient overlaps with six out of the seven pre... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2577468 Mon, 29 Jun 2009 23:00:00 +0100 2577468 http://www.medworm.com/index.php?rid=2543357&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19545651%26dopt%3DAbstract We report a familial Sotos syndrome in two children, boy and girl, aged 17 and 8 years, and in their 44 year old mother, who displayed normal intelligence at adult age, but suffered from insulin dependent diabetes mellitus, bronchial asthma, and severe lipedema. The underlying missense mutation, C2175S, occurred in a conserved segment of the NSD1 gene. Our findings confirm that familial cases of SS are more likely to carry missense mutations. This case report may prove useful to avoid underestimation of the recurrence rate of SS, and to demonstrate that the developmental delay may normalize, enabling an independent life and having an own family. PMID: 19545651 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543357 Thu, 18 Jun 2009 23:00:00 +0100 2543357 http://www.medworm.com/index.php?rid=2543360&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19505601%26dopt%3DAbstract Authors: Schluth-Bolard C, Delobel B, Sanlaville D, Boute O, Cuisset JM, Sukno S, Labalme A, Duban-Bedu B, Plessis G, Jaillard S, Dubourg C, Henry C, Lucas J, Odent S, Pasquier L, Copin H, Latour P, Cordier MP, Nadeau G, Till M, Edery P, Andrieux J Investigations of apparently balanced chromosomal rearrangements in patients with abnormal phenotype by molecular cytogenetics tools, especially by array CGH, revealed a proportion of unsuspected imbalances. It was estimated recently that 40% of apparently balanced de novo translocations with abnormal phenotype were associated with cryptic deletion. We explored 47 unrelated mental retardation patients carrying an apparently balanced chromosomal rearrangement with high-resolution oligonucleotides arrays. We included 33 de novo cases (21 trans... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543360 Fri, 05 Jun 2009 23:00:00 +0100 2543360 http://www.medworm.com/index.php?rid=2543366&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19467348%26dopt%3DAbstract Authors: Beaujard MP, Chantot S, Dubois M, Keren B, Carpentier W, Mabboux P, Whalen S, Vodovar M, Siffroi JP, Portnoï MF Despite the heterogeneous clinical presentations, the majority of patients with 22q11.2 deletion syndrome (22q11.2 DS) have either a common recurrent 3 Mb deletion or a less common, 1.5 Mb nested deletion, with breakpoint sites in flanking low-copy repeats (LCR) sequences. Only a small number of atypical deletions have been reported and precisely defined. Haploinsufficiency of the TBX1 gene was determined to be the likely cause of 22q11.2 DS. The diagnostic procedure usually used is FISH using commercially probes (N25 or TUPLE1). However, this test does not contain TBX1, and fails to detect deletions that are either proximal or distal to the FISH probes. Here, w... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543366 Fri, 22 May 2009 23:00:00 +0100 2543366 http://www.medworm.com/index.php?rid=2543364&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19467349%26dopt%3DAbstract Authors: Chistiakov DA, Voronova NV, Chistiakov AP Ligase IV (LIG4) syndrome belongs to the group of hereditary disorders associated with impaired DNA damage response mechanisms. Subjects affected with this rare autosomal recessive disease exhibit microcephaly, unusual facial features, growth retardation, developmental delay, skin anomalies, and are typically pancytopenic. The disease is characterized by pronounced radiosensitivity, genome instability, malignancy, immunodeficiency, and bone marrow abnormalities. LIG4 syndrome results from mutations in the DNA ligase IV gene encoding an enzyme that plays a pivotal role in repairing double strand DNA breaks and V(D)J recombination. Since LIG4 null-mutant mice are embryonic lethal and biallelic null mutations have not been described to da... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543364 Fri, 22 May 2009 23:00:00 +0100 2543364 http://www.medworm.com/index.php?rid=2543374&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19464395%26dopt%3DAbstract Authors: Klaassens M, de Klein A, Tibboel D Congenital diaphragmatic hernia (CDH) is a severe birth defect characterized by a defect in the diaphragm associated with pulmonary hypoplasia and postnatal pulmonary hypertension. Half of the cases present with other non-pulmonary congenital anomalies (so called non-isolated CDH) and in 5-10% of cases there is a chromosomal etiology. The clinical aspects of CDH are well documented but knowledge on the etiology of CDH is largely lacking. Worldwide many researchers have focused research efforts on CDH. Their findings have led to several hypotheses proposing roles for genetic and environmental factors. In this review we have combined these findings with our own research on the genetics of CDH in results from recent literature and propose a theo... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543374 Wed, 20 May 2009 23:00:00 +0100 2543374 http://www.medworm.com/index.php?rid=2543372&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19464396%26dopt%3DAbstract Authors: Ciotti P, Garuti A, Gulli R, Ballestrero A, Bellone E, Mandich P von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign tumours, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic tumours. The current study investigated the occurrence of VHL mutations in Italian patients with classic VHL disease or with atypical VHL-like clinical features referred to the Service of Medical Genetics for VHL molecular diagnosis. In addition, an RQ-PCR protocol was validated in order to introduce it in the routine VHL laboratory diagnosis. PMID: 19464396 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543372 Wed, 20 May 2009 23:00:00 +0100 2543372 http://www.medworm.com/index.php?rid=2543370&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19464397%26dopt%3DAbstract Authors: Stattin EL, Lindén B, Lönnerholm T, Schuster J, Dahl N Brachydactyly type A1 (BDA1; MIM 112500) is characterized by shortness or absence of the middle phalanx of the hands and feet. The condition is caused by heterozygous mutations in the Indian hedgehog (IHH) gene or a yet unidentified gene on chromosome 5p13. We investigated six affected members of a large Swedish family segregating autosomal dominant brachymesophalangia. Affected individuals show hypoplasia of the ulnar styloid processes, ulna minus, osteoarthritis, normal length of all distal phalanges and shortening or absence of the middle phalanges. Stationary ossicles or sesamoid bones were observed at the metacarpal heads in all patients. Genetic analysis of the family showed that the IHH-gene was linked to ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543370 Wed, 20 May 2009 23:00:00 +0100 2543370 http://www.medworm.com/index.php?rid=2543368&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19464398%26dopt%3DAbstract Authors: Verheij JB, de Munnik SA, Dijkhuizen T, de Leeuw N, Olde Weghuis D, van den Hoek GJ, Rijlaarsdam RS, Thomasse YE, Dikkers FG, Marcelis CL, van Ravenswaaij-Arts CM Chromosome analysis in two young patients with multiple congenital anomalies revealed a de novo interstitial deletion of 8q that has not been reported before. The deletions were overlapping by 8.35 Mb (8q24.21q24.23). The clinical features shared by our patients were coloboma, VSD, digital abnormalities, congenital dislocation of a hip, feeding problems, psychomotor delay and convulsions. The deletion included the region for Langer-Giedion syndrome (TRPS1 and EXT1) in the girl only. However, she is too young to present features of this syndrome, apart from dysmorphic features like a bulbous nose and notched alae nasi... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543368 Wed, 20 May 2009 23:00:00 +0100 2543368 http://www.medworm.com/index.php?rid=2543378&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19460468%26dopt%3DAbstract Authors: Li F, Lisi EC, Wohler ES, Hamosh A, Batista DA An inherited, interstitial subtelomere deletion of approximately 1.3-1.4 Mb at 3q29 was identified in a patient and his father utilizing BAC array comparative genomic hybridization (a-CGH). The imbalance was located within the common 3q29 microdeletion syndrome region and shared the distal breakpoint with prior published cases. However, our patient was developmentally normal at 6 months of age and his father is a functional adult, who had mild developmental delay in childhood. They presented with congenital cardiac defects including patent ductus arteriosus. In addition, the patient had subvalvular aortic stenosis and his father had pulmonic stenosis. These defects were not present in most of the previously reported 3q29 microdele... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543378 Mon, 18 May 2009 23:00:00 +0100 2543378 http://www.medworm.com/index.php?rid=2543376&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19460469%26dopt%3DAbstract Authors: Uzumcu A, Karaman B, Toksoy G, Uyguner ZO, Candan S, Eris H, Tatli B, Geckinli B, Yuksel A, Kayserili H, Basaran S Moebius syndrome is a rare disorder primarily characterized by congenital facial palsy, frequently accompanied by ocular abduction anomalies, and occasionally associated with orofacial, limb and musculoskeletal malformations. Abnormal development of cranial nerves V through XII underlines the disease pathogenesis. Although some investigations suggested that a causative gene may lie on 13q12.2-q13, there have been no molecular studies targeting possible microdeletions in this region to date. In the present study, we performed microdeletion analyses on 13q12.11-q13 in nine patients, and sequenced three candidate genes in nineteen patients for functional relevance an... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543376 Mon, 18 May 2009 23:00:00 +0100 2543376 http://www.medworm.com/index.php?rid=2543383&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454328%26dopt%3DAbstract Authors: Cau M, Loi M, Melis M, Congiu R, Loi A, Meloni C, Serrenti M, Addis M, Melis MA Cerebral cavernous malformations (CCMs) are CNS vascular anomalies associated with seizures, headaches and hemorrhagic strokes and represent 10-20% of cerebral lesions. CCM is present in 0.1-0.5 of the population. This disorder most often occurs sporadically but may also be familial. Familial cases are inherited as a dominant trait with incomplete penetrance and are estimated to account for KRIT1 10-40% of the patients. The identification of the genes involved in such disorders allows to characterize carriers of the mutations without clear symptoms. The first gene involved in CCM1 is KRIT1. In addition to two other genes have been described: MGC4607 (CCM2) and PDCD10 (CCM3). We selected 13 patients... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543383 Sun, 17 May 2009 23:00:00 +0100 2543383 http://www.medworm.com/index.php?rid=2543381&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454329%26dopt%3DAbstract CONCLUSIONS: These data highlight the difficulty of performing an appropriate test aimed at looking for cryptic 22q13.3 deletion. Furthermore, the molecular characterization of this interstitial 22q13.3 deletion contributes to the clinical and genetic delineation of the 22q13.3 deletion syndrome. PMID: 19454329 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543381 Sun, 17 May 2009 23:00:00 +0100 2543381 http://www.medworm.com/index.php?rid=2543391&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19401242%26dopt%3DAbstract We report an original observation of hereditary leukonychia totalis in a father and two of his children, associated with acanthosis-nigricans-like lesions and hair dysplasia. These symptoms were also present in eight other members of the same family. PMID: 19401242 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543391 Sun, 03 May 2009 23:00:00 +0100 2543391 http://www.medworm.com/index.php?rid=2543389&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19410022%26dopt%3DAbstract Authors: Stoll C, Alembik Y, Dott B, Roth MP Esophageal atresia is a common type of congenital malformation. The etiology of esophageal atresia is unclear and its pathogenesis is controversial. Because previous reports have inconsistently noted the type and frequency of malformations associated with esophageal atresia, we conducted this study in a geographically well-defined population, evaluating the birth prevalence of esophageal atresia and associated malformations ascertained between 1979 and 2003 in 334,262 consecutive births. Of the 99 patients with esophageal atresia, 46 (46.5%) had associated malformations. These included patients with chromosomal abnormalities (8 patients, 8%); non-chromosomal recognized syndromes (4 patients), including one each CHARGE syndrome, Fanconi anemi... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543389 Sat, 02 May 2009 23:00:00 +0100 2543389 http://www.medworm.com/index.php?rid=2543387&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19416762%26dopt%3DAbstract We report on a patient with LEOPARD syndrome and normal intelligence who was found to carry a novel sequence change in BRAF. The mutation p.L245F was demonstrated to be de novo with no evidence of somatic mosaicism. This observation illustrates that the phenotypic spectrum caused by BRAF mutations is broader than previously assumed and that mental retardation is not necessarily associated. We speculate that the impact of p.L245F on BRAF protein function differs either qualitatively or quantitatively from those mutations associated with CFCS. PMID: 19416762 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543387 Sat, 02 May 2009 23:00:00 +0100 2543387 http://www.medworm.com/index.php?rid=2543385&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19416763%26dopt%3DAbstract We report on siblings with probable Adams-Oliver syndrome. The older brother had symmetric intra-uterine growth retardation, plagiocephaly, a cardiac defect and periventricular calcification. The younger sister was born with abdominal and scalp skin defects and small fingers and toes. Prenatal cranial imaging in the younger sibling suggested possible bilateral closed lip schizencephaly and neuronal migrational defect. These siblings are thought to have Adams-Oliver syndrome with the older sibling's features at the milder end of the spectrum while the younger sibling is more severely affected. Several case reports have been published discussing the clinical variability and the possibility of autosomal recessive inheritance. Recently reports suggest an increased frequency of seizures and cen... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543385 Sat, 02 May 2009 23:00:00 +0100 2543385 http://www.medworm.com/index.php?rid=2543393&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19379847%26dopt%3DAbstract Authors: Haddad MR, Mignon-Ravix C, Cacciagli P, Mégarbané A, Villard L Moderate mental retardation (MR) could affect up to 3% of the general population. A proportion of these cases has a genetic origin. Genes responsible for mental retardation can be identified taking advantage of familial cases or patients carrying a chromosomal rearrangement. We have studied a female patient with mild mental retardation and dysmorphic features. Cytogenetic and molecular investigations revealed a de novo balanced translocation 46, XX, t(5;18)(q21.3;q21.32) in the patient. The karyotypes of the parents are normal. We mapped the breakpoints of the translocation on chromosomes 5 and 18 by fluorescence in situ hybridization (FISH). The characterization of the chromosomal breakpoints helped us i... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543393 Fri, 17 Apr 2009 23:00:00 +0100 2543393 http://www.medworm.com/index.php?rid=2543399&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19375526%26dopt%3DAbstract Authors: Polityko AD, Khurs OM, Kulpanovich AI, Mosse KA, Solntsava AV, Rumyantseva NV, Naumchik IV, Liehr T, Weise A, Mkrtchyan H An unusual mosaic karyotype was detected in a 6-year-old female patient with clinical diagnosis of Turner syndrome (TS). Cytogenetic and molecular cytogenetic studies revealed besides a cell line with 45,X a second cell line where the short arm of the Y-chromosome was translocated onto the short arm of a chromosome 7; karyotype: 45,X,der(7)t(Y;7)(p11.1 approximately 11.2;p22.3)/45,X. To delineate the mechanisms of rearrangement and karyotypic evolution in this case, further studies were performed. A maternal origin of the X-chromosome and biparental origin of both chromosomes 7 were determined by microsatellite analysis. Furthermore, using parental-origin-d... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543399 Wed, 15 Apr 2009 23:00:00 +0100 2543399 http://www.medworm.com/index.php?rid=2543397&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19375527%26dopt%3DAbstract Authors: Wright EM, O'Connor R, Kerr BA CHARGE syndrome affects up to 1 in 8500 births, and is most commonly due to de novo truncating mutations in the CHD7 gene. In addition to the 4 major (choanal atresia, coloboma, cranial nerve dysfunction and characteristic ear abnormalities) and 7 minor features (genital hypoplasia, developmental delay, cardiac anomalies, growth retardation, orofacial clefting, tracheo-oesophageal fistula and characteristic facies) proposed by Blake et al. [K.D. Blake, S.L.H. Davenport, B.D. Hall, M.A. Hefner, R.A. Pagon, M.S. Williams, A.E. Lin, J.M. Graham Jr., CHARGE association: an update and review for the primary pediatrician, Clin. Pediatr. (Phila) 37 (1998) 159-173.], many different features have been described in affected patients. Limb defects do not fe... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543397 Wed, 15 Apr 2009 23:00:00 +0100 2543397 http://www.medworm.com/index.php?rid=2543395&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19375528%26dopt%3DAbstract Authors: Ammar-Khodja F, Faugère V, Baux D, Giannesini C, Léonard S, Makrelouf M, Malek R, Djennaoui D, Zenati A, Claustres M, Roux AF A systematic approach, involving haplotyping and genotyping, to the molecular diagnosis of non-syndromic deafness within 50 families and 9 sporadic cases from Algeria is described. Mutations at the DFNB1 locus (encompassing the GJB2 and GJB6 genes) are responsible for more than half of autosomal recessive prelingual non-syndromic deafness in various populations. A c.35delG mutation can account for up to 85% of GJB2 mutations and two large deletions del(GJB6-D13S1830) and del(GJB6-D13S1854) have also been reported in several population groups. In view of the genetic heterogeneity a strategy was developed which involved direct analysis of DFNB1.... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543395 Wed, 15 Apr 2009 23:00:00 +0100 2543395 http://www.medworm.com/index.php?rid=2543401&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19371797%26dopt%3DAbstract We describe two female siblings with SWS born from consanguineous Gypsy parents. For a further delineation of SWS, we report hypothyroidism and ectopic thyroid as part of its phenotypic spectrum. Molecular study in the leukemia inhibitory factor receptor (LIFR) gene (OMIM *151 443) demonstrated the presence of a mutation. We observed that in one of our patients, oropharyngeal disruption in the swallowing process caused repetitive aspiration pneumonias, life-threatening events, and finally death. We emphasize that these features represent dysautonomic manifestations of SWS, and are probably related to pharyngoesophageal dyskinesia due to abnormal autonomic control of the anterior rami of cervical roots C1-C5. PMID: 19371797 [PubMed - as supplied by publisher] (Source: European Journal o... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543401 Mon, 13 Apr 2009 23:00:00 +0100 2543401 http://www.medworm.com/index.php?rid=2543403&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19362174%26dopt%3DAbstract Authors: Hochstenbach R, van Binsbergen E, Engelen J, Nieuwint A, Polstra A, Poddighe P, Ruivenkamp C, Sikkema-Raddatz B, Smeets D, Poot M Anomalies of chromosome number and structure are considered to be the most frequent cause of unexplained, non-syndromic developmental delay and mental retardation (DD/MR). High-resolution, genome-wide, array-based segmental aneusomy profiling has emerged as a highly sensitive technique for detecting pathogenic genomic imbalances. A review of 29 array-based studies of DD/MR patients showed that a yield of at least approximately 19% pathogenic aberrations is attainable in unselected, consecutive DD/MR referrals if array platforms with 30-70kb median probe spacing are used as an initial genetic testing method. This corresponds to roughly twice the rate... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543403 Wed, 08 Apr 2009 23:00:00 +0100 2543403 http://www.medworm.com/index.php?rid=2543405&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19361583%26dopt%3DAbstract The objective of this study was to estimate the frequency of fragile X syndrome (FXS) in mentally retarded patients from Iran. We examined a total of 508 families with MR that had been referred to the Genetics Research Center (GRC) in Tehran of which 467 families had at least two mentally retarded children. In 384 families, the parents were related and in 124 they were not related of which most of them had putative or established X-linked inheritance pattern. Full FMR1 mutations were found in 32 of the 508 families studied (6.3%), in 19 out of 124 families with apparently unrelated parents (15.3%), and in 13 of the 384 consanguineous families (3.4%). Thus, in Iran, the relative frequency of FXS seems to be high, and in patients with unrelated parents is much higher. We also show that even ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2543405 Tue, 07 Apr 2009 23:00:00 +0100 2543405 http://www.medworm.com/index.php?rid=2321067&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19328872%26dopt%3DAbstract We describe nine cases with a microdeletion at 15q11.2 between BP1-BP2, thus having a haploinsufficiency for TUBGCP5, NIPA1, NIPA2, and CYFIP1 without Prader-Willi/Angelman syndrome. The clinical significance of a pure BP1-BP2 microdeletion has been debated, however, our patients shared several clinical features, including delayed motor and speech development, dysmorphisms and behavioural problems (ADHD, autism, obsessive-compulsive behaviour). Although the deletion often appeared to be inherited from a normal or mildly affected parent, it was de novo in two cases and we did not find it in 350 healthy unrelated controls. Our results suggest a pathogenic nature for the BP1-BP2 microdeletion and, although there obviously is an incomplete penetrance, they support the existence of a novel micr... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2321067 Fri, 27 Mar 2009 04:00:00 +0100 2321067 http://www.medworm.com/index.php?rid=2321066&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19332160%26dopt%3DAbstract We report a child with a 785 kb deletion of the 3p14.1p13 region including the genes FOXP1, EIF4E3, PROK2, GPR27 resulting in speech delay, contractures, hypertonia and blepharophimosis. FOXP1 and FOXP2 are transcription factors containing a polyglutamine tract and a forkhead DNA binding domain. They both play a role in the developing human foregut and brain [14,16,18]. Mutations in FOXP2 are known to cause severe speech and language abnormalities [8] in humans and animals. It has been suggested that overlap of FOXP1 and FOXP2 expression in the songbird and human brain may indicate that mutations in FOXP1 would also result in speech and language abnormalities. The roles of EIF4E3, PROK2 and GPR27 are also evaluated. PMID: 19332160 [PubMed - as supplied by publisher] (Source: European J... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2321066 Fri, 27 Mar 2009 04:00:00 +0100 2321066 http://www.medworm.com/index.php?rid=2321065&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19332161%26dopt%3DAbstract Authors: Saadi A, Borck G, Boddaert N, Chekkour MC, Imessaoudene B, Munnich A, Colleaux L, Chaouch M Homozygous mutations in the ASPM gene are a major cause of autosomal recessive primary microcephaly (MCPH). Here we report on a consanguineous Algerian family in which three out of five children presented with severe microcephaly, simplified cortical gyration, mild to severe mental retardation and low to low-normal birth weight. Given the parental consanguinity with the unaffected parents being third cousins once removed, the most probable pattern of inheritance was autosomal recessive. Linkage and mutational analyses identified compound heterozygous truncating mutations within the ASPM gene segregating with MCPH (c.2389C > T [p.Arg797X] and c.7781_7782delAG [p.Gln2594fsX6]). These r... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2321065 Fri, 27 Mar 2009 04:00:00 +0100 2321065 http://www.medworm.com/index.php?rid=2321068&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19328248%26dopt%3DAbstract Authors: Raas-Rothschild A, Dijkhuizen T, Sikkema-Raddatz B, Werner M, Dagan J, Abeliovich D, Lerer I Nablus mask-like facial syndrome (NMFLS) is a rare microdeletion syndrome with a mask-like facial appearance as the most characteristic feature. In 2000, Teebi, was the first to report on a 4 years old boy affected with NMFLS. Since then two additional patients have been reported. Three years later, with the development of the array CGH technology, Shieh et al., elucidated the etiology of NMFLS by showing that the two patients studied share a approximately 4Mb microdeletion in the long arm of chromosome 8 (q21.3-q22.1). Here we report on two NMFLS patients among which the first patient described by Teebi in 2000, and present newly described clinical findings including the common happy ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2321068 Thu, 26 Mar 2009 04:00:00 +0100 2321068 http://www.medworm.com/index.php?rid=2321070&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19324102%26dopt%3DAbstract We describe a de novo 3q27.3q29 deletion in a 2.5-year-old female patient with developmental and growth delay, dysmorphic facial features, mild tricuspid valve dysplasia, bifid thumb, clinodactyly of the 2nd toe bilaterally and scoliosis. The deletion overlaps for about 1Mb with the 1.6Mb region commonly deleted in patients with 3q29 microdeletion syndrome. The phenotype of the two syndromes is not completely overlapping, though the most important clinical features, such as mental retardation and microcephaly, occur in both. This suggests that the deletion in our patient causes a distinct clinical phenotype, not described previously. In the deleted region there are 47 annotated genes. Among them, seven are of particular interest for correlation with clinical features of the patient. Two ge... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2321070 Tue, 24 Mar 2009 04:00:00 +0100 2321070 http://www.medworm.com/index.php?rid=2321069&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19324103%26dopt%3DAbstract Authors: van Ravenswaaij-Arts CM, Kleefstra T PMID: 19324103 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2321069 Tue, 24 Mar 2009 04:00:00 +0100 2321069 http://www.medworm.com/index.php?rid=2294133&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19306953%26dopt%3DAbstract Authors: Bijlsma EK, Gijsbers AC, Schuurs-Hoeijmakers JH, van Haeringen A, Fransen van de Putte DE, Anderlid BM, Lundin J, Lapunzina P, Jurado LA, Delle Chiaie B, Loeys B, Menten B, Oostra A, Verhelst H, Amor DJ, Bruno DL, van Essen AJ, Hordijk R, Sikkema-Raddatz B, Verbruggen KT, Jongmans MC, Pfundt R, Reeser HM, Breuning MH, Ruivenkamp CA Array CGH (comparative genomic hybridization) screening of large patient cohorts with mental retardation and/or multiple congenital anomalies (MR/MCA) has led to the identification of a number of new microdeletion and microduplication syndromes. Recently, a recurrent copy number variant (CNV) at chromosome 16p11.2 was reported to occur in up to 1% of autistic patients in three large autism studies. In the screening of 4284 patients with MR/MCA with ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2294133 Fri, 20 Mar 2009 04:00:00 +0100 2294133 http://www.medworm.com/index.php?rid=2294135&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19303466%26dopt%3DAbstract Authors: Antonietta MM, Tjitske K, Eleni K, Tiziana PF, Monika C, Rolph P, Francesca A, Ilaria M, Francesca M, Alessandra R Only two patients with 14q12 deletion have been reported to date. Here, we describe an additional patient with a similar deletion in order to improve the clinical delineation of this new microdeletion syndrome. The emerging phenotype is characterized by a Rett-like clinical course with an almost normal development during the first months of life followed by a period of regression. A peculiar facial phenotype is also present and it is characterized by mild dysmorphisms such as downslanting palpebral fissures, bilateral epicanthic folds, depressed nasal bridge, bulbous nasal tip, tented upper lip, everted lower lip and large ears. The relationship between this micro... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2294135 Thu, 19 Mar 2009 04:00:00 +0100 2294135 http://www.medworm.com/index.php?rid=2294136&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19303465%26dopt%3DAbstract Authors: Willemsen MH, de Leeuw N, Pfundt R, de Vries BB, Kleefstra T Clinical and molecular characteristics of two patients with a 6.75 Mb overlapping interstitial deletion in the 8p12p21 region are described and compared with previously reported cases with an overlapping deletion. The most common characteristics of interstitial deletions of proximal 8p are developmental delay, postnatal microcephaly and growth retardation. Other frequently reported findings are hypogonadism associated with haploinsufficiency of GNRH1 and ocular problems. Congenital heart anomalies are also common and might at least to some extent be due to haploinsufficiency of NKX2-6 or NRG1. The aforementioned clinical characteristics should be considered in the care of patients with a proximal interstitial 8p12p21... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2294136 Wed, 18 Mar 2009 04:00:00 +0100 2294136 http://www.medworm.com/index.php?rid=2294134&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19303467%26dopt%3DAbstract We report a child with Frank-ter Haar syndrome presenting unusual clinical features. Hypopigmented areas in hair, bilateral adducted thumb, bilateral contractures in elbows and pelvic limb, atrial septal defect have not been described previously in the literature. Our patient also had double-outlet right ventricle. PMID: 19303467 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2294134 Wed, 18 Mar 2009 04:00:00 +0100 2294134 http://www.medworm.com/index.php?rid=2281601&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19298871%26dopt%3DAbstract We report on a patient with a de novo microdeletion 3q29 detected by molecular karyotyping using Array CGH analysis. The girl displayed microphthalmia and cataract, hyperplastic pyloric stenosis, mild dysmorphic facial features, and developmental delay. Array CGH analysis uncovered a 1.6 Mb deletion within chromosome band 3q29, which overlaps with the commonly deleted region in 3q29 microdeletion syndrome. According to published data, none of the patients with deletion 3q29 showed either congenital cataract and microphthalmia, or other ocular features. Our report expands the phenotypic spectrum of the 3q29 microdeletion syndrome by adding structural eye malformations. PMID: 19298871 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2281601 Mon, 16 Mar 2009 04:00:00 +0100 2281601 http://www.medworm.com/index.php?rid=2281596&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19298872%26dopt%3DAbstract This report on two additional patients with this microdeletion syndrome emphasizes the rather constant and uniform phenotype encountered in this disorder and refines the critical region to a 2.61 Mb interval on 12q14.3, encompassing 10 RefSeq genes. We have previously shown that LEMD3 haploinsufficiency is responsible for the Buschke-Ollendorff lesions and provide now strong evidence that a heterozygous deletion of HMGA2 is causing the growth failure observed in this disorder. The identification of an intragenic HMGA2 deletion in a boy with proportionate short stature and the cosegregation of this deletion with reduced adult height in the extended family of the boy further underscore the role of HMGA2 in regulating human linear growth. PMID: 19298872 [PubMed - as supplied by publisher]... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2281596 Mon, 16 Mar 2009 04:00:00 +0100 2281596 http://www.medworm.com/index.php?rid=2272271&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19285578%26dopt%3DAbstract Authors: Mhatre AN, Janssens S, Nardi MA, Li Y, Lalwani AK A kindred with inherited macrothrombocytopenia (MTCP) and sensorineural hearing loss (SNHL) from Ghent, Belgium was identified. Currently, joint expression of MTCP and hearing loss are linked to mutations within MYH9 only. Thus, we tested the hypothesis that a mutation within MYH9 is responsible for the autosomal dominant inheritance of MTCP and hearing loss in the Ghent family. A mutation screen of MYH9 coding region including its intron-exon junctions, as well as common hearing loss genes GJB2, GJB3, and GJB6, was performed. However, no pathogenic sequence alteration was identified. Patients's leukocytes were determined to be normal for NMMHC-A distribution via immunofluorescence analysis and free of Döhle body-like incl... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2272271 Wed, 11 Mar 2009 04:00:00 +0100 2272271 http://www.medworm.com/index.php?rid=2255651&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19269353%26dopt%3DAbstract We report on a female patient with XY sex reversal with clitoromegaly, neonatal male testosterone and AMH levels, and a normal urine steroid profile. Array CGH revealed a de novo microdeletion of chromosome 9q33.3, including the NR5A1 gene. NR5A1 encodes for the steroidogenic factor-1 (SF-1) and heterozygous mutations in this gene were recently identified as an important cause of XY sex reversal. However, a deletion of NR5A1 has only been reported once. Patients with a mutation in NR5A1, have severe underandrogenisation with mild testicular dysgenesis. Müllerian structures may be present, while postnatal testosterone levels may be normal. This points towards a predominantly early embryonic effect of low, local, androgen levels, with or without reduced AMH levels. We recommend not only... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2255651 Thu, 05 Mar 2009 05:00:00 +0100 2255651 http://www.medworm.com/index.php?rid=2232687&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19254783%26dopt%3DAbstract Authors: Portnoï MF The chromosome 22q11.2 region has long been implicated in genomic diseases. The low-copy repeats spanning the region predispose to homologous recombination events, and mediate nonallelic homologous recombinations that result in rearrangements of 22q11.2. Chromosome duplication of the region that is deleted in patients with DGS/VCFS has been reported, establishing a new genomic duplication syndrome complementary to the 22q11.2 deletion syndrome. Recent data suggest that the frequency of the microduplications 22q11.2 is approximately half that of the deletions. Up till now about 50 unrelated cases of 22q11.2 duplications have been reported. A high frequency of familial duplications has been reported. The phenotype of patients is extremely variable, ranging from m... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2232687 Fri, 27 Feb 2009 05:00:00 +0100 2232687 http://www.medworm.com/index.php?rid=2232686&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19254784%26dopt%3DAbstract Authors: Pedace L, Castori M, Binni F, Pingi A, Grammatico B, Scommegna S, Majore S, Grammatico P Anophthalmia/microphthalmia is a rare developmental craniofacial defect, which recognizes a wide range of causes, including chromosomal abnormalities, single-gene mutations as well as environmental factors. Heterozygous mutations in the SOX2 gene are the most common monogenic form of anophthalmia/microphthalmia, as they are reported in up to 10-15% cases. Here, we describe a sporadic patient showing bilateral anophthalmia/microphthalmia and micropenis caused by a novel mutation (c.59_60insGG) in the SOX2 gene. Morphological and endocrinological evaluations excluded any anomaly of the hypothalamus-pituitary axis. Our finding supports the hypothesis that SOX2 is particularly prone to slipped... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2232686 Fri, 27 Feb 2009 05:00:00 +0100 2232686 http://www.medworm.com/index.php?rid=2232688&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19249392%26dopt%3DAbstract We present 14 new 7q11.23 cases with the reciprocal duplication of the Williams-Beuren syndrome critical region, nine familial and five de novo. These were identified by either array-based MLPA or by array-CGH/oligonucleotide analysis in a series of patients with idiopathic mental retardation with an estimated population frequency of 1:13.000-1:20.000. Variable speech delay is a constant finding in our patient group, confirming previous reports. Cognitive abilities range from normal to moderate mental retardation. The association with autism is present in five patients and in one father who also carries the duplication. There is an increased incidence of hypotonia and congenital anomalies: heart defects (PDA), diaphragmatic hernia, cryptorchidism and non-specific brain abnormalities on MRI... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2232688 Thu, 26 Feb 2009 05:00:00 +0100 2232688 http://www.medworm.com/index.php?rid=2232689&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19248844%26dopt%3DAbstract Authors: Wincent J, Schulze A, Schoumans J Bergman et al. (1) performed a search for single exon deletions or duplications in the CHD7 gene using multiplex ligation-dependent probe amplification (MLPA) in 54 CHARGE syndrome patients who did not have a CHD7 mutation. They found a deletion of exons 13-38 in one patient with a typical CHARGE syndrome phenotype (Verloes' diagnostic criteria) (2), while no exon copy number alterations were identified in 36 atypical CHARGE syndrome patients. On this basis, Bergman et al recommended to extend testing using MLPA solely in individuals with a typical CHARGE syndrome phenotype. PMID: 19248844 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2232689 Tue, 24 Feb 2009 05:00:00 +0100 2232689 http://www.medworm.com/index.php?rid=2216634&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19236961%26dopt%3DAbstract We describe a patient with an abnormal phenotype and a de novo CCR consisting of a reciprocal translocation between chromosomes 1 and 15 and an insertion of an interstitial segment from chromosome 2 within chromosome 1. The CCR was studied by QFQ banding and FISH. The apparently balanced rearrangement was further investigated with array-CGH, that uncovered three cryptic deletions on chromosome 2q. By means of BAC-FISH two deletions were located at the breakpoints of the insertion, at 2q14.3 and 2q31.2, and one at 2q22.2, in the region of 2q translocated on derivative 1. Consequently, in silico analysis of the deleted regions was performed. Among deleted genes, particularly interesting seems to be CNTNAP5, encoding a member of the neurexin superfamily. The three mouse orthologues are highly... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2216634 Fri, 20 Feb 2009 05:00:00 +0100 2216634 http://www.medworm.com/index.php?rid=2210550&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19233320%26dopt%3DAbstract We report on a patient with a microdeletion of chromosome region 9q22.32q31.1 including the PTCH1 gene (human homologue of the Drosophila patched 1 gene), review the findings in the reported patients with similar array CGH findings, and highlight the non nevoid basal cell carcinoma/ non-Gorlin syndrome findings at an earlier age. These are macrocephaly, neonatal hypotonia, severe psychomotor retardation with markedly delayed motor milestones and speech development, epicanthic folds, a thin upper lip, a short and wide/webbed neck, pectus excavatum and (kypho)scoliosis. These features should alert the physician to an early diagnosis of the microdeletion and allow the initiation of essential clinical management hereof. PMID: 19233320 [PubMed - as supplied by publisher] (Source: European J... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2210550 Thu, 19 Feb 2009 05:00:00 +0100 2210550 http://www.medworm.com/index.php?rid=2210549&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19233321%26dopt%3DAbstract Authors: Van Esch H, Backx L, Pijkels E, Fryns JP The recurrent microdeletion 15q24 syndrome is rare with only 5 cases reported thus far. Here we describe an additional patient with this deletion, presenting with many features common to this syndrome, including developmental delay, loose connective tissue, digital and genital anomalies and a distinct facial gestalt. Interestingly, in addition, this patient has a large congenital diaphragmatic hernia, as was described in one other patient with a 15q24 microdeletion, indicating that this feature might be part of the syndrome. Chromosome 15q24 has a highly polymorphic architecture that is prone to genomic rearrangements underlying this novel microdeletion syndrome. PMID: 19233321 [PubMed - as supplied by publisher] (Source: European J... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2210549 Thu, 19 Feb 2009 05:00:00 +0100 2210549 http://www.medworm.com/index.php?rid=2210548&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19233322%26dopt%3DAbstract Authors: Kalender AM, Dogan A, Sebik A, Gokalp MA PMID: 19233322 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2210548 Thu, 19 Feb 2009 05:00:00 +0100 2210548 http://www.medworm.com/index.php?rid=2104531&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19138766%26dopt%3DAbstract CONCLUSIONS: Large scale DNA rearrangements (such as large deletions) and cryptic splice mutations, that can be missed on standard sequencing of genomic DNA, may be relatively common in POMT2. Additional techniques, such as sequencing of cDNA are needed to identify all mutations. These results also confirm that POMT2 mutations are an important cause of the less severe alpha-dystroglycanopathy phenotypes. PMID: 19138766 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2104531 Sat, 27 Dec 2008 05:00:00 +0100 2104531 http://www.medworm.com/index.php?rid=2104530&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19138767%26dopt%3DAbstract We report a 5-year-old child presenting sparse hair, reduced sweating, ice-pick skin depressions of the dorsum of hands, facial and limb milia, perianal skin hyperpigmentation, and hyperpigmented papules of the axillae and neck. His mother showed similar features but lacked hair involvement. Histologic examination of a skin papule obtained from the index case revealed features consistent with trichoepithelioma. Our findings indicate that trichoepitheliomas are an early sign of Bazex-Dupré-Christol syndrome and may guide the diagnosis even before the development of basal cell carcinomas. The high frequency of hypotrichosis, hypohidrosis and dry skin in Bazex-Dupré-Christol syndrome indicates that it may be better classified as an ectodermal dysplasia. Comparison with other conditi... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2104530 Thu, 25 Dec 2008 05:00:00 +0100 2104530 http://www.medworm.com/index.php?rid=2074192&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19116176%26dopt%3DAbstract Authors: Girirajan S, Elsea SH The retinoic acid induced 1 gene (RAI1) is the primary causative gene for Smith-Magenis syndrome (SMS). Chromosomal deletion encompassing RAI1 or mutations in RAI1 is responsible for the majority of SMS features. Mouse models with targeted disruption of Rai1 have recapitulated overt SMS phenotypes, including craniofacial abnormalities, obesity, and neurobehavioral anomalies. Penetrance and expressivity of most phenotypes in mice were incomplete due to the mixed genetic background in which they were created. While increased penetrance of craniofacial phenotypes was observed in relatively homogeneous backgrounds, the effect of Rai1 haploinsufficiency on breeding outcome and fitness has not been studied. We analyzed mating results of Rai1(+/-) mice in a pure... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2074192 Wed, 24 Dec 2008 05:00:00 +0100 2074192 http://www.medworm.com/index.php?rid=2067440&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19110080%26dopt%3DAbstract We report the first case of a boy with clinical features of AAS with deletion of FGD1 gene identified using an oligonucleotide-based X chromosome-specific microarray after attempts to generate amplicons for all of the FGD1 coding exons failed and BAC microarray analysis showed no abnormality. PMID: 19110080 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2067440 Tue, 16 Dec 2008 05:00:00 +0100 2067440 http://www.medworm.com/index.php?rid=2060995&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19100872%26dopt%3DAbstract We report a 3.1-Mb de novo deletion of 3p21.31 in a 3.5-year-old female with cortical blindness, cleft lip, CNS abnormalities, and gross developmental delays. Examination of the region showed approximately 80 genes to be involved in the deletion. Functional analysis of the deleted genes suggests that several of them may be important in normal neuronal maturation and function. Thus, haploinsufficiency of one or more of these genes could potentially contribute to the observed phenotype. Our patient does not have clinical features that overlap completely with either proximal or distal 3p deletions, suggesting that the deletion seen in our patient leads to a distinct clinical phenotype not described previously. PMID: 19100872 [PubMed - as supplied by publisher] (Source: European Journal of... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2060995 Sat, 13 Dec 2008 05:00:00 +0100 2060995 http://www.medworm.com/index.php?rid=2060994&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19101659%26dopt%3DAbstract We report a novel large deletion in DFNB1 observed in a patient presenting profound prelingual HI. This deletion was observed in trans to a GJB2 mutated allele carrying the p.Val84Met (V84M) mutation and was shown to be associated with hearing loss. The deletion caused a false homozygosity of V84M in the proband. Quantification of alleles by quantitative fluorescent multiplex PCR (QFM-PCR) enabled us to study the breakpoints of the deletion. The deleted segment extended through at least 920kb and removed the three connexin genes GJA3, GJB2 and GJB6. The distal breakpoint inside intron 2 of CRYL1 gene differed from the breakpoints of the known DFNB1 deletions. This case highlights the importance of screening for large deletions in molecular studies of GJB2. PMID: 19101659 [PubMed - as s... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2060994 Sat, 13 Dec 2008 05:00:00 +0100 2060994 http://www.medworm.com/index.php?rid=2027069&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19059503%26dopt%3DAbstract We report two families in which the probands have compound-heterozygous Marfan syndrome (MFS). The proband of family 1 has the R2726W FBN1 mutation associated with isolated skeletal features on one allele and a pathogenic FBN1 mutation on the other allele. The phenotype of the compound-heterozygous probands appears to be more severe than that of their heterozygous family members which underlines the possibility that certain trans-located FBN1 mutations might act as modifiers of phenotype explaining some of the intrafamilial variability in Marfan syndrome. PMID: 19059503 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2027069 Thu, 27 Nov 2008 05:00:00 +0100 2027069 http://www.medworm.com/index.php?rid=2011138&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19049908%26dopt%3DAbstract We report an 18-gestational-week fetus with oligohydramnios, orofacial clefting, bilateral multicystic kidneys and the Dandy-Walker malformation. Characteristic craniofacial features include a turricephalic prominent forehead, hypertelorism, low-set ears, a flat nasal bridge, mid-face hypoplasia, bilateral cleft lip and palate, and a thick nuchal fold. Array-comparative genomic hybridization (CGH) analysis demonstrated a 12Mb deletion of 6p24.1-->pter. PMID: 19049908 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2011138 Wed, 19 Nov 2008 05:00:00 +0100 2011138 http://www.medworm.com/index.php?rid=2005822&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19041736%26dopt%3DAbstract Authors: Poot M, Van't Slot R, Leupert R, Beyer V, Passarge E, Haaf T A 32-year-old female patient, observed for 30 years because of a distinctive phenotype consisting of a dysmorphic face non-progressive deficit of motor control, lack of speech development, reduced sensitivity to pain, with a known, complex interstitial deletion 6q14 within a de novo pericentric inversion 6p11.2;q15, was re-examined at the molecular level. Applying the Infinium HumanHap300 BeadChip array and BAC-based FISH we found two new non-contiguous microdeletions in addition to the one detected previously by high resolution G-band analysis. A 360 kb loss in band 6p12.3, containing the genes RHAG, CRISP1, 2, and 3, and PGK2, a 1.15 Mb loss in 6p12.2-p12.1, containing the genes PKHD1, IL17, MCM3, EFHC1, and TRAM2 ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2005822 Wed, 19 Nov 2008 05:00:00 +0100 2005822 http://www.medworm.com/index.php?rid=2005821&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19041959%26dopt%3DAbstract In this report we present two sisters who are compound heterozygous for a premutation, and who were referred because of very early menopause, occurring at the age of 17 years in the youngest sister. Premature ovarian failure associated with FMR1 premutation at such an early age has not been reported in the literature before. PMID: 19041959 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2005821 Mon, 17 Nov 2008 05:00:00 +0100 2005821 http://www.medworm.com/index.php?rid=2005820&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19041960%26dopt%3DAbstract We describe the molecular characterization by FISH and array CGH of this unusual inv dup del (8p) and a previously reported patient with a similar 8q duplication and review the literature on cases associated with telomere capture. PMID: 19041960 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2005820 Mon, 17 Nov 2008 05:00:00 +0100 2005820 http://www.medworm.com/index.php?rid=2005823&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19041432%26dopt%3DAbstract We report on a 4-month-old Chinese male infant who presented with a severe BSCL "cardiac" phenotype comprising heart failure, hypertension and hypertrophic cardiomyopathy. PMID: 19041432 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=2005823 Wed, 12 Nov 2008 05:00:00 +0100 2005823 http://www.medworm.com/index.php?rid=1980686&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19022412%26dopt%3DAbstract We report on clinical and molecular findings of two brothers that both presented with sagittal craniosynostosis, hydrocephalus, Chiari I malformation, blepharophimosis, small low-set ears, hypoplastic philtrum, radioulnar synostosis, kidney malformation, and hypogenitalism. Their father presented mild brachydactyly. Conventional cytogenetic and array CGH screening did not show any chromosomal gains or losses. Furthermore, molecular genetic screening of genes involved in different craniosynostosis syndromes, namely FGFR1, FGFR2, FGFR3, TWIST, RECQL4, and POR genes failed to detect any mutations in genomic DNA. The unique range of clinical manifestations in these two patients and the negative findings of the molecular genetic screening suggest the hypothesis of a previously unrecognized synd... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1980686 Thu, 06 Nov 2008 05:00:00 +0100 1980686 http://www.medworm.com/index.php?rid=1975123&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19015050%26dopt%3DAbstract We report a 22-year-old man with PEO and optic atrophy. PEO developed before the onset of optic atrophy. The patient showed mitochondrial myopathy with cytochrome c oxidase deficient fibers. In skeletal muscle the patient was homoplasmic for the mtDNA G11778A Leber hereditary optic neuropathy (LHON) mutation and heteroplasmic for the mtDNA 5kb "common" deletion mutation. In blood only the homoplasmic LOHN mutation was identified. The occurrence of two pathogenic mtDNA mutations is exceedingly rare. The clinical findings in this patient indicate that the combination of the two mtDNA mutations resulted in the expected combined phenotype since the mtDNA deletion mutation accounted for the PEO and the mtDNA G11778A point mutation for the optic atrophy. PMID: 19015050 [PubMed - as supplied ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1975123 Wed, 05 Nov 2008 05:00:00 +0100 1975123 http://www.medworm.com/index.php?rid=1951898&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18992376%26dopt%3DAbstract We report here the case of a 10-year-old female with a de novo 7. 8Mb deletion in the 6q13-6q14.1 ascertained by array-CGH. The clinical features of this patient include psychomotor and language delay associated with minor dysmorphic features. PMID: 18992376 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1951898 Tue, 21 Oct 2008 04:00:00 +0100 1951898 http://www.medworm.com/index.php?rid=1939122&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18983945%26dopt%3DAbstract We describe an additional case, a 7-year-old boy with profound mental retardation, severe microcephaly, facial dysmorphism, symphalangism, contractures of large joints, hyperopia, strabismus, bilateral conductive hearing loss, genital abnormality, psoriasis vulgaris and tracheo-esophageal fistula. Analysis with whole-genome SNP genotyping assay detected a 5.9Mb deletion in chromosome band 17q22-q23.2 with breakpoints between 48,200,000-48,300,000bp and 54,200,000-54,300,000bp (according to NCBI 36). The aberration was confirmed by real-time quantitative PCR analysis. Haploinsufficiency of NOG gene has been implicated in the development of conductive hearing loss, skeletal anomalies including symphalangism, contractures of joints, and hyperopia in our patient and may also contribute to the ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1939122 Fri, 17 Oct 2008 04:00:00 +0100 1939122 http://www.medworm.com/index.php?rid=1939121&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18984066%26dopt%3DAbstract We report on a three-generation family with five affected individuals and male-to-male transmission. In addition to widespread keratosis pilaris, cicatricial alopecia and eye involvement, our patients show diffuse facial erythema, recurrent folliculitis, enamel hypoplasia, and thickened nails. A literature review of the last 50 years identified 43 additional KFSD cases. X-linked inheritance is demonstrated in two pedigrees by linkage studies and suspected in five. An autosomal dominant pattern is confirmed in three families, including ours, by male-to-male transmission and considered likely in four. Marked facial erythema, extensive folliculitis, onychodystrophy and multiple caries are frequently reported in the autosomal dominant variant, while palmo-plantar keratoderma and early onset se... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1939121 Fri, 17 Oct 2008 04:00:00 +0100 1939121 http://www.medworm.com/index.php?rid=1876070&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18848651%26dopt%3DAbstract This report illustrates the practical benefits associated with a clear cytogenetic diagnosis, as regular endocrinological and cardiac screening is required. PMID: 18848651 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1876070 Fri, 19 Sep 2008 04:00:00 +0100 1876070 http://www.medworm.com/index.php?rid=1859544&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18834961%26dopt%3DAbstract Authors: Liu C, Shen A, Li X, Jiao W, Zhang X, Li Z Despite animal studies having demonstrated that Tbx20 is essential for heart development, few studies have been conducted about TBX20 and congenital heart disease (CHD) in humans. Recently two TBX20 mutations have been associated with human heart defects in two Caucasian families, but TBX20 mutations underlying the more common isolated forms of CHD are still unknown. To explore this question and to analyze the association between TBX20 and susceptibility to CHD 203 Chinese patients with a variety of predominantly sporadic CHD and 300 control subjects were investigated for TBX20 mutations. The exon 2-6 contributing to the T-box DNA-binding domain and their flanking intron sequences were amplified by polymerase chain reaction (PCR) and ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1859544 Fri, 12 Sep 2008 04:00:00 +0100 1859544 http://www.medworm.com/index.php?rid=1841040&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18822396%26dopt%3DAbstract We report on a patient with a de novo del(2) (q36.2q36.3) interstitial deletion of the long arm of chromosome 2 diagnosed by classical banding. The phenotype comprised facial dysmorphism, enlarged kidneys with multiple renal cysts, abnormal minora labia, asymmetric lower limbs with dysplastic patella, and severe mental retardation. By physical mapping, using array-comparative genomic hybridisation (CGH) confirmed by Fluorescent In Situ Hybridisation (FISH), the breakpoints of the deletion were mapped and the size of the deletions was measured: 5.61+/-0.19Mb. A skin biopsy was analysed using electronic microscopy showing an alteration of the structure and organisation of the dermal and peri-neuronal basement membrane. The relation between the phenotype and the deletion of both COL4A4 and CO... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1841040 Sat, 06 Sep 2008 04:00:00 +0100 1841040 http://www.medworm.com/index.php?rid=1798168&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18790721%26dopt%3DAbstract Authors: Kaya N, Al-Owain M, Albakheet A, Colak D, Al-Odaib A, Imtiaz F, Coskun S, Al-Sayed M, Al-Hassnan Z, Al-Zaidan H, Meyer B, Ozand P Propionic acidemia is a metabolic disorder (OMIM 606054) caused by deficiency of the propionyl-coenzyme A (CoA) carboxylase, which subsequently results in accumulation of propionic acid. Patients may initially present with poor feeding, vomiting, loss of appetite, hypotonia, and lethargy. Later, most children will show different degrees of motor, social and language delay even more serious medical problems, including heart abnormalities, seizures, coma, and possibly death. Two siblings affected with propionic acidemia were screened for putative mutations in PCCA and PCCB genes coding alpha and beta subunits of propionyl-coenzyme A (CoA) carboxylase,... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1798168 Tue, 26 Aug 2008 04:00:00 +0100 1798168 http://www.medworm.com/index.php?rid=1779255&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18775522%26dopt%3DAbstract We report a child presenting with Alagille and Wolff-Parkinson-White (WPW) syndromes. Standard karyotyping showed a de novo 46,XY,t(1;6)(p31;q16) translocation. Fluorescent in situ hybridization analysis identified a de novo deletion in the 20p12 chromosomal region encompassing JAG1, the major gene responsible for Alagille syndrome. The aberration was further characterized using an Agilent 44K oligonucleotide array, which confirmed the 4.95Mb 20p12 deletion. An additional 8.26Mb deletion was identified at the 6q16 translocation breakpoint. To our knowledge, WPW has never been associated with Alagille syndrome. The patient we describe presented with a 6q16 deletion containing 21 genes but no good candidate genes for WPW. The 20p12 deletion included 19 genes among them JAG1 and BMP2. Recentl... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1779255 Fri, 15 Aug 2008 04:00:00 +0100 1779255 http://www.medworm.com/index.php?rid=1759916&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18762283%26dopt%3DAbstract Authors: Ginocchio VM, De Brasi D, Genesio R, Ciccone R, Gimelli S, Fimiani F, de Berardinis T, Nitsch L, Banfi S, Magli A, Della Casa R About 20% of cases with 7q deletion syndrome is associated with holoprosencephaly (HPE), due to deletion of the Sonic Hedgehog (SHH) gene (mapping to 7q36). The occurrence of severe forms of holoprosencephaly is higher in cases of 7q deletion associated with partial trisomies involving different parts of the genomes than in patients with pure 7q deletion. All cases of 7q deletion associated with 3p duplication reported to date have been associated with severe forms of holoprosencephaly, and a gene(s) on distal 3p has (have) been hypothesized to be responsible for HPE phenotype when in triple dose. Here we describe a patient with unbalanced 3p;7q trans... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1759916 Wed, 13 Aug 2008 04:00:00 +0100 1759916 http://www.medworm.com/index.php?rid=1754725&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18757044%26dopt%3DAbstract We report on a healthy man with high normal intelligence, minor dysmorphic features and infertility due to hypergonadism and azoospermia. Cytogenetic analysis showed a 6.7Mb duplication in chromosome band 11q24.2q25, which could be confirmed with FISH and molecular karyotyping using an Affymetrix GeneChip Mapping 250K Nsp SNP array. PMID: 18757044 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1754725 Tue, 12 Aug 2008 04:00:00 +0100 1754725 http://www.medworm.com/index.php?rid=1754724&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18757045%26dopt%3DAbstract We report on a child with mild mental retardation, hypotelorism, blepharophimosis, face slight asymmetry and partial hypoplasia of corpus callosum, with an interstitial deletion of a chromosome 15. The deletion was molecularly characterized by array-CGH and FISH techniques. This rearrangement has a 7.18Mb extension and maps to 15q21.2q22.1. To date, there have been only six individuals reported with a deletion of 15q21; in three cases, the rearrangement was characterized by molecular cytogenetic techniques. After a comparison with these three cases, it appeared that the deletion we found is one of the smallest and it overlaps the distal portion of the ones taken into account. Finally, we tried to delineate the genotype-phenotype correlation in patients with a deletion of 15q21. PMID: 1... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1754724 Tue, 12 Aug 2008 04:00:00 +0100 1754724 http://www.medworm.com/index.php?rid=1746115&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18755302%26dopt%3DAbstract Authors: Kiholm Lund AB, Hove HD, Kirchhoff M A 15q24 microduplication, reciprocal to the minimal critical region for the recently described 15q24 microdeletion syndrome, was found in a 2-year-old boy by 244k Agilent oligoarray CGH analysis. The boy had global developmental delay and dysmorphic facial features, digital and genital abnormalities. The duplication was inherited from a healthy father, but was considered clinically significant, as the patient shared clinical features with 15q24 microdeletion syndrome patients. To our knowledge this is the first report of a patient with a 15q24 microduplication. PMID: 18755302 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1746115 Thu, 07 Aug 2008 04:00:00 +0100 1746115 http://www.medworm.com/index.php?rid=1746116&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18725332%26dopt%3DAbstract We report two new patients with the 1.4Mb recurrent 22q11.2 distal deletion syndrome. Features common to both children, as well as to several of the previously reported cases, include normal palate, smooth philtrum, hypoplastic alae nasi and delayed development. Both children are small but not growth retarded, and are microcephalic. Their developmental delay is global and most pronounced for language acquisition. One child has unilateral sensorineural hearing loss and encopresis, and the other child has treatment-responsive nocturnal epileptogenic activity. These two new cases confirm the recurrent nature of the deletion and help to further delineate the phenotype. PMID: 18725332 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1746116 Tue, 05 Aug 2008 04:00:00 +0100 1746116 http://www.medworm.com/index.php?rid=1746117&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18721913%26dopt%3DAbstract We describe a previously unreported, typically affected two-month-old girl with this microdeletion syndrome, who additionally suffers from left-ventricular non-compaction (LVNC). Recently, this congenital heart defect, characterized by prominent left-ventricular trabeculae and deep intertrabecular recesses, was reported in 12 further patients (excluding those reported only in abstract form) with terminal deletion of 1p36, leading to the conclusion that this cardiomyopathy is common in patients with this chromosomal aberration [Battaglia A, Hoyme HE, Dallapiccola B, Zackai E, Hudgins L, McDonald-McGinn D, Bahi-Buisson N, Romano C, Williams CA, Braley LL, Zuberi SM, Carey JC, Further delineation of deletion 1p36 syndrome in 60 patients: a recognizable phenotype and common cause of developmen... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1746117 Thu, 31 Jul 2008 04:00:00 +0100 1746117 http://www.medworm.com/index.php?rid=1717188&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18707033%26dopt%3DAbstract In this study we present two familial cases with a 3Mb 22q11.2 duplication detected by array-CGH. We also review the findings in 36 reported cases with the aim of delineating the phenotype of the 22q11.2 duplication syndrome. In a majority of the reported cases where parents have been tested, the duplication seems to have been inherited from a normal parent with minor abnormalities. With this in mind we recommend that family members of patients with a 22q11.2 duplication to be tested for this genetic defect. PMID: 18707033 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1717188 Tue, 29 Jul 2008 04:00:00 +0100 1717188 http://www.medworm.com/index.php?rid=1717189&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18706534%26dopt%3DAbstract Authors: Rittinger O, Kronberger G, Pfeifenberger A, Kotzot D, Fauth C Diploid/triploid mosaicism is a rare chromosome aberration characterized by growth and mental retardation, muscular hypotonia, clinodactyly, syndactyly of fingers and toes, asymmetry of the body and the face, truncal obesity, and pigmentary anomalies of the skin. Many patients initially present with severe growth retardation and develop truncal obesity later in life. Variable phenotype expression during development and restriction of triploid cells to certain tissues explain why the diagnosis of diploid/triploid mosaicism is often delayed. Here, we report on a moderately retarded 14-year-old girl with diploid/triploid mosaicism due to inclusion of the second polar body, whose changing phenotype overlaps considerably... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1717189 Sat, 26 Jul 2008 04:00:00 +0100 1717189 http://www.medworm.com/index.php?rid=1700722&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18692163%26dopt%3DAbstract This report emphasizes the importance to distinguish proximal 15q polymorphic variants from clinically significant duplications. In any patient with inherited 15q proximal variant but unexplained developmental delay suggesting 15q11-q13 pathology, a pathogenic rearrangement has to be searched with adapted strategies, in order to detect deletions as well as duplications of this region. PMID: 18692163 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1700722 Tue, 22 Jul 2008 04:00:00 +0100 1700722 http://www.medworm.com/index.php?rid=1700723&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691679%26dopt%3DAbstract Authors: Faas BH, Nillesen W, Vermeer S, Weghuis DO, de Leeuw N, Smits AP, van Ravenswaaij-Arts CM It is known from postnatal diagnosis that imbalances of the subtelomeric regions contribute significantly to idiopathic mental retardation. Consequently, subtelomere screening has been incorporated into the recommendations for the evaluation of individuals with unexplained mental retardation and a normal karyotype. Previous studies suggested that for fetuses with ultrasound abnormalities and a normal karyotype, additional screening for submicroscopic imbalances can be relevant for diagnosis and prognosis. In the present paper, we report the detection of such (subtelomeric) imbalances in three fetuses. Prenatally, the three fetuses presented with ultrasound abnormalities were highly suspec... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1700723 Sat, 19 Jul 2008 04:00:00 +0100 1700723 http://www.medworm.com/index.php?rid=1686257&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18678287%26dopt%3DAbstract Authors: Ferrero GB, Baldassarre G, Delmonaco AG, Biamino E, Banaudi E, Carta C, Rossi C, Silengo MC Noonan syndrome (NS, OMIM 163950) is an autosomal dominant disorder, with a prevalence at birth of 1:1000-1:2500 live births, characterized by short stature, facial and skeletal dysmorphisms, cardiovascular defects and haematological anomalies. Missense mutations of PTPN11 gene account for approximately 50% of NS cases, while molecular lesions of other genes of the RAS/MAPK pathway -KRAS, SOS1 and RAF1 - play a minor role in the molecular pathogenesis of the disease. Forty patients were enrolled in the study with a PTPN11 mutation detection rate of 31.5%, including a novel missense mutation, Phe285Ile, in a familial case with high intrafamilial phenotype variability. All patients negati... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1686257 Thu, 17 Jul 2008 04:00:00 +0100 1686257 http://www.medworm.com/index.php?rid=1683021&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18675946%26dopt%3DAbstract Authors: Poot M, Kroes HY, Hochstenbach R PMID: 18675946 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1683021 Wed, 16 Jul 2008 04:00:00 +0100 1683021 http://www.medworm.com/index.php?rid=1683020&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18675947%26dopt%3DAbstract Authors: Rossi E, Verri AP, Patricelli MG, Destefani V, Ricca I, Vetro A, Ciccone R, Giorda R, Toniolo D, Maraschio P, Zuffardi O An interstitial deletion of about 12Mb at 7q33-q36 was found in an adult female affected by autism and primary amenorrhea. Two genes, CNTNAP2 and NOBOX, both contained within the deletion region, have been recently associated with autism susceptibility and premature ovarian failure, respectively. Our findings reinforce the hypothesis that haploinsufficiency of both these genes is sufficient for autism development and occurrence of primary amenorrhea, confirming a previous case in which CNTNAP2 had been disrupted by a chromosome inversion and possibly enlarging the phenotype of ovarian function disturbances already demonstrated for NOBOX mutations. PMID: ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1683020 Wed, 16 Jul 2008 04:00:00 +0100 1683020 http://www.medworm.com/index.php?rid=1683025&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18674645%26dopt%3DAbstract We describe a partial duplication of the chromosome 16 short arm [46,XY,dup(16)(p11.2p13.1)] in an Iranian girl with autism, neurodevelopmental delay, mental retardation, very poor memory, and dysmorphism including sparse hair, upslanting palpebral fissures, long philtrum, micrognathia, hypotonia, small feet and hands, syndactyly of the fingers, and hypoplastic thumbs. The patient now four years old, has a normal twin sister, and the parents are unrelated. The abnormal 16p was originally detected by banding cytogenetic techniques, and was characterized by multicolour banding fluorescence in situ hybridization (MCB). The MCB pattern on the derivative chromosome 16 indicated a direct duplication of the region 16p11.2 to 16p13.1. PMID: 18674645 [PubMed - as supplied by publisher] (Source:... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1683025 Sat, 12 Jul 2008 04:00:00 +0100 1683025 http://www.medworm.com/index.php?rid=1683024&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18674646%26dopt%3DAbstract Authors: Cardoso LC, Moraes L, Camilo MJ, Mulatinho MV, Ramos H, Almeida JC, Llerena JC, Seuánez HN, Vargas FR We studied a child with apparent monosomy of chromosome 21. Cytogenetic, FISH and microsatellite analyses revealed a 45,X,-21,+der(X)t(X;21)(q25;q21.1) karyotype resulting from a de novo, unbalanced, X;21 non-reciprocal translocation of paternal origin, with partial monosomy of chromosomes 21 and X. An extreme, skewed X-inactivation pattern of the der(X) chromosome was demonstrated. Skewed inactivation probably accounted for a mild phenotype with respect to Xq25-->qter deletion while propagation of inactivation to the adjacent 21q region may account for mild clinical features associated to distal 21q monosomy. PMID: 18674646 [PubMed - as supplied by publisher] (Sou... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1683024 Sat, 12 Jul 2008 04:00:00 +0100 1683024 http://www.medworm.com/index.php?rid=1683023&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18674647%26dopt%3DAbstract We report on a 26-year-old woman with microcephaly, typical facial features of 9q subtelomeric deletion syndrome, exophthalmos, contractures of elbow and knee joints, severe muscular hypotonia, no ability to walk, and no speech development. Array CGH revealed a cryptic 9q34.3 deletion and 2p25.2-p25.3 duplication transmitted by her mother, who was carrying a balanced translocation of chromosomes 2p and 9q. There are about 50 reported cases of deletions of the subtelomeric part of chromosome 9q, however, duplications of only the terminal part of chromosome 2p are rare. Neuroblastoma, diaphragmatic hernia, neural tube defects, broncho-pulmonary abnormalities, and congenital heart defects are conditions associated with partial trisomy of larger fragments of 2p. To our knowledge there is only ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1683023 Sat, 12 Jul 2008 04:00:00 +0100 1683023 http://www.medworm.com/index.php?rid=1683022&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18674648%26dopt%3DAbstract We report a familial case of pericentric inversion of chromosome 19 not detectable by standard karyotype and usual subtelomeric FISH probes. This inversion was transmitted in its balanced and in its recombinant form to the offspring. The two children carrying the recombinant chromosome 19 presented with growth and mental retardation, microcephaly, mild facial dysmorphism and clinodactyly. The recombinant chromosome 19 was characterized by FISH and array CGH. It consisted of a 400kb 19pter deletion and a 6.9Mb (19q13.33-qter) duplication. This observation supports the recombination risk of pericentric inversion of chromosome 19 and emphasizes the role of molecular cytogenetics techniques in the characterization of chromosome 19 rearrangements. PMID: 18674648 [PubMed - as supplied by pub... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1683022 Sat, 12 Jul 2008 04:00:00 +0100 1683022 http://www.medworm.com/index.php?rid=1674882&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18672102%26dopt%3DAbstract Authors: Zhang W, Li X, Shen A, Jiao W, Guan X, Li Z Recent studies have reported germline mutations in GATA4 gene in some types of congenital heart disease (CHD). However, the prevalence of GATA4 mutations in CHD and the correlation between the GATA4 genotype and CHD phenotype have not been extensively studied. We screened germline mutations in the coding exons and the flanking intron sequences of the GATA4 gene in 486 CHD patients by denaturing high-performance liquid chromatography (DHPLC), and confirmed the mutations by sequencing. Nine distinct mutations including one small deletion mutation (46delS), two small insertion mutations (118-119insA and 125-126insAA), and six non-synonymous mutations (A6V, P163S, E359K, P407Q, S429T and A442V) were identified in 12 of the 486 patients (... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1674882 Fri, 11 Jul 2008 04:00:00 +0100 1674882 http://www.medworm.com/index.php?rid=1674881&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18672103%26dopt%3DAbstract In conclusion, this study illustrates the complexity of such rearrangement characterized by array CGH and strengthens that constitutional 1p36.3 rearrangement predisposes to the development of neuroblastoma. PMID: 18672103 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1674881 Fri, 11 Jul 2008 04:00:00 +0100 1674881 http://www.medworm.com/index.php?rid=1664293&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18657636%26dopt%3DAbstract In this study, a novel EDA mutation (Thr338Met) that results in X-linked non-syndromic hypodontia in a Chinese family was identified. The patterns of tooth agenesis in these related subjects with defined EDA mutation were analyzed using comparative statistical analysis of tooth agenesis in EDA, MSX1 and PAX9. Statistically significant differences (p<0.001) were observed at eight positions. The resulting data of congenital absence of maxillary and mandibular central incisors, lateral incisors and canines, with the high possibility of persistence of maxillary and mandibular first permanent molars, appears as a pattern of tooth agenesis, suggesting the presence of an EDA mutation. PMID: 18657636 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1664293 Wed, 09 Jul 2008 04:00:00 +0100 1664293 http://www.medworm.com/index.php?rid=1664292&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18657637%26dopt%3DAbstract Authors: Mencarelli MA, Katzaki E, Papa FT, Sampieri K, Caselli R, Uliana V, Pollazzon M, Canitano R, Mostardini R, Grosso S, Longo I, Ariani F, Meloni I, Hayek J, Balestri P, Mari F, Renieri A The introduction of array-CGH analysis is allowing the identification of novel genomic disorders. However, this new high-resolution technique is also opening novel diagnostic challenges when inherited private CNVs of unclear clinical significance are found. Oligo array-CGH analysis of 84 patients with mild to severe mental retardation associated with multiple congenital anomalies revealed 10 private CNVs inherited from a healthy parent. Three were deletions (7q31, 14q21.1, Xq25) and seven duplications (12p11.22, 12q21.31, 13q31.1, 17q12, Xp22.31, Xq28) ranging between 0.1 and 3.8Mb. Six rearrang... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1664292 Wed, 09 Jul 2008 04:00:00 +0100 1664292 http://www.medworm.com/index.php?rid=1664294&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18655849%26dopt%3DAbstract Authors: Kotzot D Maternal uniparental disomy (UPD) 7 is found in approximately 5% of patients with Silver-Russell syndrome. By a descriptive and comparative clinical analysis of all published cases (more than 60 to date) their phenotype is updated and compared with the clinical findings in patients with Sliver-Russell syndrome (SRS) of either unexplained etiology or epimutations of the imprinting center region 1 (ICR1) on 11p15. The higher frequency of relative macrocephaly and high forehead/frontal bossing makes the face of patients with epimutations of the ICR1 on 11p15 more distinctive than the face of cases with SRS of unexplained etiology or maternal UPD 7. Because of the distinct micrognathia in the latter, their triangular facial gestalt is more pronounced than in the other gro... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1664294 Fri, 04 Jul 2008 04:00:00 +0100 1664294 http://www.medworm.com/index.php?rid=1577316&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18595793%26dopt%3DAbstract CONCLUSIONS: An AluYa5 insertion (c.1657ALUYa5ins, p.Thr553_Pro597del) in exon 11 of the GAN gene was identified homozygous in both siblings, whereas the parents were heterozygous carriers of this mutation. Here, the reported mutation is located in C-terminal part of the protein affecting the terminal kelch domain. Thus a functional important part of the protein is altered by the AluYa5 insertion and causes GAN. PMID: 18595793 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1577316 Tue, 17 Jun 2008 04:00:00 +0100 1577316 http://www.medworm.com/index.php?rid=1560858&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18585117%26dopt%3DAbstract Authors: Schöherr N, Jäger S, Ranke MB, Wollmann HA, Binder G, Eggermann T Imprinting defects have meanwhile been described in nearly all human imprinting disorders among them Silver-Russell syndrome (SRS). In this disorder, 11p15 epimutations and maternal Uniparental Disomy of chromosome 7 (UPD7) are detectable in approximately 50% of patients. To find out whether isolated imprinting defects on chromosome 7 play a role in the aetiology of SRS we screened a cohort of 54 SRS patients without 11p15 epimutations. Methylation-specific PCR was carried out for the PEG1/MEST locus in 7q31. This test detects all known segmental and complete UPD7 cases. The exclusion of isolated imprinting defects in our study population shows that this type of epimutation at the PEG1/MEST locus in 7q... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1560858 Fri, 23 May 2008 04:00:00 +0100 1560858 http://www.medworm.com/index.php?rid=1560857&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18586597%26dopt%3DAbstract Authors: Concolino D, Muzzi G, Pisaturo L, Piccirillo A, Di Natale P, Strisciuglio P To date the association between mucopolysaccharidosis (MPS) IIIA and precocious puberty has been found in only three polish patients. We observed two children affected by MPS IIIA with central precocious puberty (CPP) both treated with GnRH agonists. The occurrence of CPP in both patients with MPS IIIA suggests that it is necessary to look for an association between the two conditions. The follow-up of our two patients leads us to believe also that GnRH agonist treatment can have a beneficial effect on final height and probably on the improvement of behavioural problems. PMID: 18586597 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1560857 Fri, 23 May 2008 04:00:00 +0100 1560857 http://www.medworm.com/index.php?rid=1516538&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18547887%26dopt%3DAbstract This study underscores the value of combining conventional karyotyping with novel array technologies to unravel complex chromosomal alterations in order to study their phenotypic impact. PMID: 18547887 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1516538 Sat, 03 May 2008 04:00:00 +0100 1516538 http://www.medworm.com/index.php?rid=1508400&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18539553%26dopt%3DAbstract We report here a three generations family with nevoid basal cell carcinoma syndrome (NBCCS) in which the diagnosis was made only after a second trimester of pregnancy ultrasonography revealing fetal cranio-cerebral malformations. A mutation was subsequently characterized in the aborted fetus, as well as in the mother, sister and grand-mother as an 18bp deletion in exon 15 of the patched homologue 1 (PTCH1) gene. MC1R gene sequencing identified in two NBCCS patients affected by multiple basal cell carcinomas a functional MC1R variant, D294H, previously shown to be associated with skin cancer risk. This variant was absent in the NBCCS patient that did not develop basal cell carcinomas, suggesting that this variant could have favored the development of skin cancers, in patients carrying the P... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1508400 Fri, 02 May 2008 04:00:00 +0100 1508400 http://www.medworm.com/index.php?rid=1469694&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18501694%26dopt%3DAbstract We report two new female patients with typical features of Catel-Manzke syndrome (MIM 302380) and the follow-up of the first patient affected by this syndrome. In addition to the Pierre Robin anomaly, the hallmark of this palatodigital syndrome is a bilateral hyperphalangy and clinodactyly of the index finger. Classified into four groups there are now (1) 23 reported cases of the typical, (2) six cases of the extended Catel-Manzke syndrome showing more than two accessory bones in the hand, (3) two patients showing unilateral hyperphalangy and clinodactyly of the index finger (4) two patients described with isolated features of the "Manzke dysostosis" without Pierre Robin anomaly. The karyotype of our three patients was normal. A search for submicroscopic chromosomal abnormalities by array ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1469694 Fri, 11 Apr 2008 04:00:00 +0100 1469694 http://www.medworm.com/index.php?rid=1463814&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18495567%26dopt%3DAbstract We report a 12-year-old patient with Patau syndrome, in whom two cell lines were present from birth, one with total trisomy 13 due to isochromosome (13q), and one with partial trisomy 13. A cytogenetic re-evaluation at 9 years of age brought to light in skin fibroblasts a third cell line, partially monosomic for chromosome 13. The derivatives (13) present in the three cell lines were characterized through fluorescence in situ hybridization (FISH) experiments with suitable probes; the results suggested a sequence of rearrangements which beginning from an isochromosome (13q) could have led to the other two derivatives. We report the clinical data at birth and at the age of 12; at this age pigmentary lesions with phylloid pattern were noted. Cytogenetic findings of the chromosomal analyses on... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1463814 Wed, 09 Apr 2008 04:00:00 +0100 1463814 http://www.medworm.com/index.php?rid=1439589&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18472328%26dopt%3DAbstract Authors: Bergman JE, de Wijs I, Jongmans MC, Admiraal RJ, Hoefsloot LH, van Ravenswaaij-Arts CM CHARGE syndrome is a multiple congenital anomaly syndrome caused by mutations in the CHD7 gene. Mutations in this gene are found in 60-70% of patients suspected of having CHARGE syndrome. However, if only typical CHARGE patients are taken into account, mutations in the CHD7 gene are found in over 90% of cases. The remaining 10% might be caused by hitherto undetected alterations of the CHD7 gene, including whole exon duplications and deletions that are missed by the currently used diagnostic procedures. Therefore we looked for these kinds of alterations by multiplex ligation-dependent probe amplification in 54 patients suspected of having CHARGE syndrome without a CHD7 mutation. In one patien... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1439589 Fri, 04 Apr 2008 04:00:00 +0100 1439589 http://www.medworm.com/index.php?rid=1426386&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18458017%26dopt%3DAbstract We report a male patient with speech and language disorder, cleft palate, epilepsy, a ventricular septal defect, mental retardation and developmental delay. Characteristic facial features include low-set ears, a beak-like nose, a prominent nasal bridge, a long philtrum, a narrow forehead, a long face, a pointed chin and dental position abnormalities. Array-comparative genomic hybridization (CGH) analysis demonstrated the presence of a 5.6-Mb deletion in 15q14 (chromosome 15: 3,18,33,000-3,74,77,000bp). The present case provides the evidence that 15q14 deletion outside the region encompassing the CHRNA7 gene can cause generalized epilepsy, and a locus in 15q14 is associated with speech and language disorder. PMID: 18458017 [PubMed - as supplied by publisher] (Source: European Journal of... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1426386 Sat, 29 Mar 2008 04:00:00 +0100 1426386 http://www.medworm.com/index.php?rid=1406997&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18440888%26dopt%3DAbstract Authors: Utine EG, Alanay Y, Aktas D, Alikasifoglu M, Boduroglu K, Vermeesch J, Tuncbilek E, Fryns JP A 10(6/12)-year-old boy was referred to the genetics department because of mental retardation and dysmorphic findings including microcephaly, flat face, down-slanting palpebral fissures, strabismus, prominent ears, bulbous nasal tip, down-turned corners of the mouth, narrow palate, clinodactyly of the fifth fingers and generalised eczema. Cytogenetic analysis revealed a karyotype of 47,XY,+mar of paternal origin. Multicolour FISH showed the marker chromosome to be derived from chromosome 15. For further elucidation of the phenotype, array-based comparative genomic hybridisation (aCGH) was performed, which revealed dup(5)(q35.2qter) and del(1)(p36.3). Parental FISH analysis revealed tha... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1406997 Thu, 27 Mar 2008 04:00:00 +0100 1406997 http://www.medworm.com/index.php?rid=1399156&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18434272%26dopt%3DAbstract Authors: Thiel CT, Dörr HG, Trautmann U, Hoyer J, Hofmann K, Kraus C, Ekici AB, Reis A, Rauch A We delineate a pure "distal 14q duplication" phenotype, characterized by primordial short stature, mild developmental delay, and distinct facial dysmorphism with high forehead, mild hypertelorism, broad nasal bridge, dysplastic ear helices, short philtrum, thin and "cupid bow" upper lip, broad mouth, and micrognathia. PMID: 18434272 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1399156 Thu, 20 Mar 2008 04:00:00 +0100 1399156 http://www.medworm.com/index.php?rid=1399155&cid=s_35543_176_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18434273%26dopt%3DAbstract Authors: Kaisaki PJ, Bergmann C, Brown JH, Outeda P, Lens XM, Peters DJ, Gretz N, Gauguier D, Bihoreau MT Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders in humans. Although disease-causing mutations have been found in two genes, PKD1 and PKD2, a small number of ADPKD families exist that are unlinked to either of these genes, suggesting involvement of a third, as yet unidentified PKD3 gene. Susceptibility to renal cyst formation in the (cy/+) rat is caused by a missense mutation in Pkdr1 encoding the novel protein SamCystin. To initiate studies of the human orthologous gene, we determined the location and the organization of human PKDR1. We genotyped microsatellite markers flanking the human ortholog in PKD families that either are unl... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=1399155 Sun, 16 Mar 2008 04:00:00 +0100 1399155