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 'American Journal of Medical Genetics Part A' source. Thu, 09 Feb 2012 09:43:25 +0100 http://www.medworm.com/index.php?rid=5672455&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35217 AbstractThe proximal region of the long arm of chromosome 22 is rich in low copy repeats (LCR). Non‐allelic homologous recombination (NAHR) between these substrates explains the high prevalence of recurrent rearrangements within this region. We have performed array comparative genomic hybridization in a normally developing girl with growth delay, microcephaly, and truncus arteriosus, and have identified a novel recurrent 22q11 deletion that spans LCR22‐4 and partially affects the common 22q11.2 deletion syndrome and the distal 22q11 deletion syndrome. This deletion is atypical as it did not occur by NAHR between any of the major LCRs found on 22q11.2. However, the breakpoint containing regions coincide with highly homologous regions. An identical imbalance was reported previously in a ... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672455 Wed, 08 Feb 2012 05:00:00 +0100 5672455 http://www.medworm.com/index.php?rid=5672467&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35207 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672467 Tue, 07 Feb 2012 05:00:00 +0100 5672467 http://www.medworm.com/index.php?rid=5672466&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34258 We report on a 32‐month‐old Japanese girl with a unique subtype of PH, namely ribbon‐like PH. The patient presented with severe psychomotor developmental delay, intractable epilepsy, and congenital cataracts and developed West syndrome phenotype. Brain magnetic resonance imaging revealed a unique undulating form of PH, categorized as ribbon‐like PH, and other brain malformations including simplified gyri and dysgenesis of the corpus callosum. There was no evidence of prenatal TORCH infection or associated syndrome. Array‐based comparative genomic hybridization revealed no chromosomal rearrangements. Genetic analyses of the FLNA, DCX, ARX, LIS1, and TUBA1A genes showed no mutations. Although little is known about ribbon‐like PH, the clinical manifestations in our patient clearly... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672466 Tue, 07 Feb 2012 05:00:00 +0100 5672466 http://www.medworm.com/index.php?rid=5672465&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34439 We report a female NS patient carrying a PTPN11 germline mutation c.417 G > C (p.E139D), who developed in her second year of life an acute lymphoblastic leukemia (ALL) and after remission, she developed at 4 years of age a juvenile myelomonocytic leukemia (JMML). Molecular genetic analysis of lymphoblastic blasts at the time of the ALL diagnosis revealed the germline mutation in a heterozygous state, while in the myelomonocytic blasts occurring with JMML diagnosis, the mutation p.E139D was found in a homozygous state due to a uniparental disomy (UPD). These findings lead to the suggestion that the pathogenesis of ALL and JMML in our patient is due to different mechanisms including somatically acquired secondary chromosomal abnormalities. © 2012 Wiley Periodicals, Inc. (Source: Amer... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672465 Tue, 07 Feb 2012 05:00:00 +0100 5672465 http://www.medworm.com/index.php?rid=5672464&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35197 AbstractThe American Journal of Medical Genetics Part A is to be congratulated for taking a leadership role by publishing a number of papers challenging the status quo of prenatal counseling for Down syndrome and of care for children and adults with Down syndrome. Parents want to know about the future abilities and potential of their fetus with Down syndrome, not simply negative medical information that may be outdated. Those providing counseling and those providing medical care could benefit from contact with individuals with Down syndrome outside the medical context. It is imperative that each person with Down syndrome be viewed as a unique individual with particular talents. Medical care providers should work with parents to help the child or adult with Down syndrome reach his/her goals... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672464 Tue, 07 Feb 2012 05:00:00 +0100 5672464 http://www.medworm.com/index.php?rid=5672463&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35201 We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3‐q24.13. Array‐comparative genomic hybridization (a‐CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarch... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672463 Tue, 07 Feb 2012 05:00:00 +0100 5672463 http://www.medworm.com/index.php?rid=5672462&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35202 AbstractHyperphosphatasia with neurologic deficit (Mabry syndrome) was first described in a single family (OMIM#239300) by Mabry et al. [1970]. Although considered rare at the time, more than 20 individuals with the triad of developmental disability, seizures, and hyperphosphatasia have been identified world‐wide. The 1‐6 mannosyltransferase 2, phosphatidylinositol glycan V (PIGV) gene has been found to be disrupted in some patients with the additional feature of brachytelephalangy. In the present report we identify three patients compound homozygous for PIGV mutations. Two siblings were found to be compound heterozygotes for c.467G > A and c.494C > A in exon 3 of PIGV (the c.494C > A PIGV variant is novel). A third patient with similar phenotype, was a compound he... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672462 Tue, 07 Feb 2012 05:00:00 +0100 5672462 http://www.medworm.com/index.php?rid=5672461&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35204 AbstractGastroschisis is a congenital abdominal wall defect, thought by many to represent a disruption in intrauterine blood flow, where there is herniation of abdominal organs. Dietary intake is an important environmental factor that has been implicated in the development of many diseases. Omega‐6 polyunsaturated fatty acids (PUFAs) are nutrients that are substrates for eicosanoid and cytokine synthesis and prone to oxidation, and play a role in modulating inflammation, immune function, and vascular system development. This pilot case‐control study explored the association of dietary intake of the omega‐6 PUFA linoleic acid with risk of gastroschisis. Between 2008 and 2011, we recruited 13 pregnant women in mid‐gestation who were referred to the UCSD Prenatal Center for evaluation... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672461 Tue, 07 Feb 2012 05:00:00 +0100 5672461 http://www.medworm.com/index.php?rid=5672460&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35209 AbstractA child whose features are consistent with Pallister–Killian syndrome (PKS) did not have detectable tetrasomy 12p due to an additional isochromosome 12p in an unstimulated blood specimen by interphase FISH or array CGH analysis. The diagnosis of PKS was made through these methods solely in a skin biopsy specimen. To determine the sensitivity of our array CGH platform to tetrasomy 12p mosaicism, dilutions of DNA from both the child's skin fibroblasts and a PKS cell line were analyzed. Tetrasomy 12p at 10% mosaicism was identifiable but 5% was below the limit of detection. This result suggests through extrapolation that the tetrasomy 12p is present in <10% of cells in our patient's blood, confirming the tissue‐limited mosaicism of PKS. Multiple recent studies show that array C... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672460 Tue, 07 Feb 2012 05:00:00 +0100 5672460 http://www.medworm.com/index.php?rid=5672459&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35210 This study indicates that parents, whose child has been diagnosed with a birth defect, could benefit from being informed about available genetic counseling services. The results show that some non‐users of genetics services may have misconceptions about the purpose of genetic counseling and correcting these may increase utilization. This is important in order to ensure all parents receive sufficient information and support after diagnosis of a birth defect in their child. © 2012 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672459 Tue, 07 Feb 2012 05:00:00 +0100 5672459 http://www.medworm.com/index.php?rid=5672458&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35211 AbstractTo assess psychosocial functioning and quality of life in a representative group of adult and young patients with Shwachman–Diamond syndrome (SDS), all patients 3 years old and over included in the Italian SDS Registry were investigated using an ad‐hoc questionnaire for information about demography, education, socialization, rehabilitation therapy, and standardized questionnaires [SF‐36, Child Behavior Check‐List (CBCL)] for quality of life and behavior. Results were compared with those of a Cystic Fibrosis (CF) patient group, matched for age and sex. Eighty‐one percent of patients answered. All but one adult patient lived with their parents, 24% had independent income, and 57% had a driver's license. Different levels (from mild to severe) of cognitive impairment were rep... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672458 Tue, 07 Feb 2012 05:00:00 +0100 5672458 http://www.medworm.com/index.php?rid=5672457&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35215 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672457 Tue, 07 Feb 2012 05:00:00 +0100 5672457 http://www.medworm.com/index.php?rid=5672456&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35222 AbstractAlthough the relationship between meiotic recombination frequency and synaptonemal complex (SC) length has been of interest for a long time, how recombination frequency is related to SC length has not been carefully explored. To address this question, we have measured the meiotic recombination frequency as represented by MLH1 foci in 889 pachytene spermatocytes and measured the length of 19,558 autosomal SCs from 10 human males. A complex relationship between the number of MLH1 foci and total autosomal SC length per cell was observed. A positive correlation with significant correlation coefficients between the two variables was found in eight of the ten donors examined, with three donors showing weak correlation, and five showing moderate correlation. Two donors who did not show an... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672456 Tue, 07 Feb 2012 05:00:00 +0100 5672456 http://www.medworm.com/index.php?rid=5663349&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34417 We report on a consanguineous couple with two affected sons who presented with primary microcephaly and moderate to severe intellectual disabilities. A SNP array uncovered two overlapping regions of copy‐neutral absence of heterozygosity (AOH) in both sibs. This led to sequencing of WDR62, a gene that codes for a spindle pole protein recently identified as a cause of primary microcephaly. A homozygous missense mutation in WDR62, p.E400K, was found in both boys and segregated with the condition in this family. WDR62 is one of seven genes responsible for autosomal recessive primary microcephaly (MCPH), and appears to be one of the most frequently involved in MCPH following ASPM. Studies of ASPM and WDR62 should perhaps be pursued in all cases of primary microcephaly with or without gross b... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5663349 Fri, 03 Feb 2012 05:00:00 +0100 5663349 http://www.medworm.com/index.php?rid=5663348&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34426 We report on a family with features of TBS in whom a novel 149 kb deletion spanning the SALL1 gene was identified by high resolution cytogenetics SNP microarray. We review the available genotype–phenotype information for all known truncating mutations and deletions. Taken together, they do not support the correlation of SALL1 deletions with a milder TBS phenotype and highlight a need for more robust clinical phenotyping combined with investigation of mutational mechanism. © 2012 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5663348 Fri, 03 Feb 2012 05:00:00 +0100 5663348 http://www.medworm.com/index.php?rid=5663347&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34434 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5663347 Fri, 03 Feb 2012 05:00:00 +0100 5663347 http://www.medworm.com/index.php?rid=5663346&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34435 We present a boy with AOS who developed a progressive splenomegaly and hypersplenism at the age of 2 months, and was admitted for acute gastrointestinal bleeding (GI) at the age of 9 months. Subsequently, we documented an extrahepatic portal vein obstruction and esophageal varices. After several episodes of cataclysmic upper GI bleeding a mesentero‐portal shunt (MPS) was performed at 10 months. The shunt thrombosed, and after three failed attempts of thrombectomy, it was removed. One month later a splenorenal shunt was performed, and this closed spontaneously by 3 years. The patient suffered from ischemic stroke after placing the first shunt, and has spastic diplegia, left frontal lobe epilepsy, hyperactivity and attention deficit disorder, and severe psychomotor delay. At 11 years and h... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5663346 Fri, 03 Feb 2012 05:00:00 +0100 5663346 http://www.medworm.com/index.php?rid=5663345&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34437 We describe a novel inherited disorder consisting of idiopathic massive splenomegaly, cytopenias, anhidrosis, chronic optic nerve edema, and vision loss. This disorder involves three affected patients in a single non‐consanguineous Caucasian family, a mother and two daughters, who are half‐sisters. All three patients have had splenectomies; histopathology revealed congestion of the red pulp, but otherwise no abnormalities. Electron microscopic studies of splenic tissue showed no evidence for a storage disorder or other ultrastructural abnormality. Two of the three patients had bone marrow examinations that were non‐diagnostic. All three patients developed progressive vision loss such that the two oldest patients are now blind, possibly due to a cone‐rod dystrophy. Characteristics o... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5663345 Fri, 03 Feb 2012 05:00:00 +0100 5663345 http://www.medworm.com/index.php?rid=5654720&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34400 AbstractColoboma and various ocular abnormalities have been described in CHARGE syndrome, although the severity of visual impairment varies from case to case. We conducted a multicenter study to clarify the ophthalmic features of patients with molecularly confirmed CHARGE syndrome. Thirty‐eight eyes in 19 patients with CHARGE syndrome and confirmed CHD7 mutations treated at four centers were retrospectively studied. Colobomata affected the posterior segment of 35 eyes in 18 patients. Both retinochoroidal and optic disk colobomata were bilaterally observed in 15 patients and unilaterally observed in 3 patients. The coloboma involved the macula totally or partially in 21 eyes of 13 patients. We confirmed that bilateral large retinochoroidal colobomata represents a typical ophthalmic featur... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654720 Thu, 02 Feb 2012 05:00:00 +0100 5654720 http://www.medworm.com/index.php?rid=5654719&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34413 AbstractVon Recklinghausen neurofibromatosis (NF1) is an autosomal dominant disorder with a prevalence about 1/3,000 (1/2,000–1/5,000 in various population‐based studies). About 30–50% of cases are sporadic, resulting from a new mutation. NF1 is fully penetrant by mid‐childhood, stigmata, and medical problems (neurological, dermatological, endocrine, ophthalmological, oncological) are highly variable. Advanced paternal age (APA) has been known to increase the risk of new germline mutations that contribute to the presence of a variety of genetic diseases in the human population. The trend in developed countries has been toward higher parental age due to various reasons. In a cross‐sectional study, in two university hospital centers, data on parental age of 103 children (41 female)... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654719 Thu, 02 Feb 2012 05:00:00 +0100 5654719 http://www.medworm.com/index.php?rid=5654718&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34416 We report on a fetus with an isolated short femur detected by ultrasound and a de novo interstitial deletion of chromosome 15. The deletion was diagnosed prenatally by karyotype and further mapped by fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (array‐CGH) to bands 15q15.3 to 15q21.3 with a size of 11.11 Mb. Fetal autopsy showed characteristic minor anomalies, urinary abnormalities, and delayed bone maturation, but neither craniosynostosis, nor congenital heart defects as observed in previously reported cases. Despite the existence of ultrasound abnormalities, all five cases reported so far were diagnosed after birth. This is the first case of an interstitial deletion involving chromosomal band 15q15.3‐q21.3 diagnosed prenatally and characteri... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654718 Thu, 02 Feb 2012 05:00:00 +0100 5654718 http://www.medworm.com/index.php?rid=5654717&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34419 AbstractNoonan syndrome (NS) is the most common non‐chromosomal syndrome seen in children and is characterized by short stature, dysmorphic facial features, chest deformity, a wide range of congenital heart defects and developmental delay of variable degree. Mutations in the Ras/mitogen‐activated protein kinase (MAPK) signaling pathways cause about 70% of NS cases with a KRAS mutation present in about 2%. In a cohort of 65 clinically confirmed NS patients of Japanese origin, we screened for mutations in the RAS genes by direct sequencing. We found a novel mutation in KRAS with an amino acid substitution of asparagine to serine at codon 116 (N116S). We analyzed the biological activity of this mutant by ectopic expression of wild‐type or mutant KRAS. NS‐associated KRAS mutation resul... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654717 Thu, 02 Feb 2012 05:00:00 +0100 5654717 http://www.medworm.com/index.php?rid=5654716&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34420 AbstractA 9‐year‐old boy with the classical type of Ehlers–Danlos syndrome (EDS) developed a symptomatic aneurysm of the superior mesenteric artery. His EDS diagnosis had been confirmed biochemically and genetically. Vascular complications are known to be associated with the vascular type of EDS, but this is the first report of a child with classical EDS who developed a major vascular complication. Clinicians should be aware that severe vascular complications albeit rare, can also occur in classical EDS. © 2012 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654716 Thu, 02 Feb 2012 05:00:00 +0100 5654716 http://www.medworm.com/index.php?rid=5654715&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34424 We report on the clinical and radiological findings in two HCH children with a FGFR3 mutation. In both children, fetal US showed short femora and relatively increased biparietal diameter (BPD). However, postnatal assessment failed to make a specific diagnosis in the neonatal period. The correct diagnosis of HCH was accomplished by reassessment after exacerbation of postnatal short stature. In retrospective radiological review, the radiological findings relevant to HCH were discernible more easily in the neonatal period than at age of 3 years. © 2012 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654715 Thu, 02 Feb 2012 05:00:00 +0100 5654715 http://www.medworm.com/index.php?rid=5654714&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34425 This report narrows the critical region responsible for CHDs seen in 4q deletion syndrome. © 2012 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654714 Thu, 02 Feb 2012 05:00:00 +0100 5654714 http://www.medworm.com/index.php?rid=5654713&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34431 We report on a child with dextrocardia, atrial septal defect (ASD), severe developmental delay, hypotonia, 13 pairs of ribs, left preauricular choristoma, hirsutism, and craniofacial abnormalities. Prenatal cytogenetic evaluation showed karyotype 46,XY,?dup(8p)ish del(8)pter. Postnatal array CGH demonstrated a 6.8 Mb terminal deletion at 8p23.3–p23, an interstitial 31.1 Mb duplication within 8p23.1–p11, and a terminal duplication of 0.24 Mb at 22q13.33, refining the karyotype to 46,XY,der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1).ish der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1) (D8S504‐,MS607 + ,ARSA + ,D8Z1 + , RP115713 + +). Previous reports of distal 8p deletion, 8p duplication, and distal 22q duplication have shown similar manifestations, including congenital... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654713 Thu, 02 Feb 2012 05:00:00 +0100 5654713 http://www.medworm.com/index.php?rid=5654712&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34432 AbstractThis paper focuses on the influence of consanguinity on the occurrence of orofacial clefts. All patients with orofacial clefts registered at King Faisal Specialist Hospital and Research Center, Riyadh since June 1999 until December 2009 were included in this study. Patients were classified in two distinct groups: cleft lip with or without cleft palate (CL ± P) and isolated cleft palate (CP). Chi‐squared test was used to test independence of variables. Intracluster correlation coefficient was estimated to assess the degree of concordance between siblings. Among 1,171 total patients, CL ± P was found to be more common (64.0%). Males were more likely to be affected with CL ± P (M:F = 1.5:1) and females were more likely to be affected with CP (M:F = 0.9:1; P ... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654712 Thu, 02 Feb 2012 05:00:00 +0100 5654712 http://www.medworm.com/index.php?rid=5654711&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34433 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654711 Thu, 02 Feb 2012 05:00:00 +0100 5654711 http://www.medworm.com/index.php?rid=5654710&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.33958 We present two siblings with Taybi–Linder syndrome, with an emphasis on the neurological profile in this disease, which includes brain malformations, intractable epilepsy, sensory deficits, profound cognitive deficits, and neuroendocrine dysfunction. We also present distinctive correlative neuroimaging (MRI) and electroencephalographic (EEG) findings. Increased knowledge of the neurological profile of Taybi–Linder syndrome may be helpful for clinicians and genetic counselors managing these patients. © 2012 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654710 Thu, 02 Feb 2012 05:00:00 +0100 5654710 http://www.medworm.com/index.php?rid=5654709&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34221 AbstractThe deletion of the long arm of chromosome 18 causes a contiguous gene deletion syndrome with a highly variable phenotype, usually related to the extent of the deleted region. The most commonly reported clinical features include: decreased growth, microcephaly, facial abnormalities, hypotonia, developmental delay, intellectual disability, congenital aural atresia with hearing impairment and limb anomalies. Here we report on a familial terminal deletion of 18q23 region transmitted from a mother to two daughters, resulting in a remarkable phenotypic variability. The deletion was first detected by conventional cytogenetic analysis in one daughter and subsequently characterized using fluorescence in situ hybridization (FISH) and array‐CGH. FISH analysis using subtelomeric 18p and 18q... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654709 Thu, 02 Feb 2012 05:00:00 +0100 5654709 http://www.medworm.com/index.php?rid=5654708&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34430 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654708 Thu, 02 Feb 2012 05:00:00 +0100 5654708 http://www.medworm.com/index.php?rid=5654707&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34438 AbstractHydrops fetalis is an excessive accumulation of fetal fluid. Hydrops is traditionally classified into either immune or non‐immune hydrops (NIHF), but in practice, nowadays in the Western world >90% of hydrops is of non‐immune origin. The basis of the disorder is an imbalance in the regulation of fetal fluid movement between the vascular and interstitial space. We previously suggested a diagnostic flow‐chart for NIHF. In this short review we describe the main mechanisms leading to NIHF. © 2012 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654707 Thu, 02 Feb 2012 05:00:00 +0100 5654707 http://www.medworm.com/index.php?rid=5654706&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34441 AbstractThe prevalence of the 22q11.2 duplication is unknown in children with cardiovascular malformations (CVMs). As most individuals with the duplication are detected in the search for other conditions, especially the 22q11.2 deletion, CVMs associated with the duplication are subject to referral bias. We circumvented this bias by investigating the prevalence of the 22q11.2 duplication in a population‐based cohort of children with CVMs. The study population was defined as children born in 2000–2008, who were registered in the Danish National Patient Registry with a diagnosis of CVM from one of the two national university departments of pediatric cardiology. Sensitive multiplex ligation‐dependent probe amplification was performed on dried blood spot samples from each individual's neo... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654706 Thu, 02 Feb 2012 05:00:00 +0100 5654706 http://www.medworm.com/index.php?rid=5654705&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35206 We report a patient heterozygous for the mutation in ACTA2 R179H who presented with megacystis at 13 weeks gestational age and, at birth, with prune‐belly sequence. He also had deep skin dimples and creases on his palms and soles, a finding not previously described but possibly related to ACTA2. To our knowledge, this is the first report of the R179H mutation in ACTA2 in a child with prune‐belly sequence. We think the R179H mutation in ACTA2 should be included in the differential diagnosis of individuals presenting with the sequence without an identified mechanical obstruction. Furthermore, as ACTA2 R179H has been reported in patients with severe vasculomyopathy and premature death, we recommend that molecular testing for this mutation be considered in fetuses presenting with fetal meg... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654705 Thu, 02 Feb 2012 05:00:00 +0100 5654705 http://www.medworm.com/index.php?rid=5672454&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35223 We report on 57 prospectively ascertained pregnancies after maternal therapy with mycophenolate (mycophenolate mofetil or mycophenolate sodium) identified by European Teratology Information Services (ETIS) through their risk consultation process. The outcome of these prospective pregnancies was as follows: 16 spontaneous abortions, 12 elective terminations of pregnancy (ETOP) (including two late terminations for multiple malformations consistent with mycophenolate embryopathy), and 29 liveborn infants. The probability of spontaneous abortion was about 45% (95% CI 29 to 66%) estimated using survival analysis technique. Six out of 29 live born infants had major congenital defects: Two with external auditory canal atresia (EACA) (with and without microtia), one with tracheo‐esophageal atres... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5672454 Wed, 01 Feb 2012 05:00:00 +0100 5672454 http://www.medworm.com/index.php?rid=5663344&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34436 We present a mother and child with a heterozygous 365 Kb deletion at 16q24.3 containing ANKRD11, ZNF778, and SPG7 genes. The child presented with developmental delay, facial anomalies, hand anomalies, and a congenital heart defect. The mother has short stature, facial anomalies, macrodontia, hand anomalies, and learning disability. Both individuals had many findings reported in KBG syndrome and the family met the suggested diagnostic criteria. However, typical macrodontia with fused incisors, costovertebral anomalies, and delayed bone age were not present. We conclude that microdeletions involving ANKRD11 result in a phenotype similar to that of KBG syndrome. © 2012 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5663344 Wed, 01 Feb 2012 05:00:00 +0100 5663344 http://www.medworm.com/index.php?rid=5654704&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35213 AbstractIn most Western countries, information on prenatal screening for Down syndrome is provided in the first‐trimester of pregnancy. The purpose of this study was to examine whether this information should additionally be provided before pregnancy to improve the informed decision‐making process. In an empirical study, we obtained data from pregnant women with respect to their preferences regarding information on prenatal screening preconceptionally. Questionnaire data (n = 510) showed that 55.7% of responding women considered participating in prenatal screening for Down syndrome before pregnancy. 28.0% of women possessed information on prenatal screening preconceptionally. 84.6% preferred not to receive information preconceptionally in retrospect. In an ethical analysis, we elab... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5654704 Wed, 01 Feb 2012 05:00:00 +0100 5654704 http://www.medworm.com/index.php?rid=5615665&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35227 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5615665 Sat, 21 Jan 2012 14:22:25 +0100 5615665 http://www.medworm.com/index.php?rid=5615664&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35226 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5615664 Sat, 21 Jan 2012 14:22:24 +0100 5615664 http://www.medworm.com/index.php?rid=5615663&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35225 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5615663 Sat, 21 Jan 2012 14:22:23 +0100 5615663 http://www.medworm.com/index.php?rid=5615662&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35253 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5615662 Sat, 21 Jan 2012 14:22:22 +0100 5615662 http://www.medworm.com/index.php?rid=5615661&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35252 AbstractDynamic MRIs showing changes over time in 2 patients with progressive cerebellar tonsillar ectopia who have a disorder of brain overgrowth. See article by Mirzaa et al. in this issue. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5615661 Sat, 21 Jan 2012 14:22:20 +0100 5615661 http://www.medworm.com/index.php?rid=5590890&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34405 AbstractMowat–Wilson syndrome (MWS) is caused by a heterozygous mutation or deletion of the ZEB2 gene. It is characterized by a distinctive facial appearance in association with intellectual disability (ID) and variable other features including agenesis of the corpus callosum, seizures, congenital heart defects, microcephaly, short stature, hypotonia, and Hirschsprung disease. The current study investigated the behavioral phenotype of MWS. Parents and carers of 61 individuals with MWS completed the Developmental Behavior Checklist. Data were compared with those for individuals selected from an epidemiological sample of people with ID from other causes. The behaviors associated with MWS included a high rate of oral behaviors, an increased rate of repetitive behaviors, and an under‐react... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590890 Fri, 13 Jan 2012 05:00:00 +0100 5590890 http://www.medworm.com/index.php?rid=5590889&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34401 AbstractFloating‐Harbor syndrome (FHS) is characterized by characteristic facial dysmorphism, short stature with delayed bone age, and expressive language delay. To date, the gene(s) responsible for FHS is (are) unknown and the diagnosis is only made on the basis of the clinical phenotype. The majority of cases appeared to be sporadic but rare cases following autosomal dominant inheritance have been reported. We identified a 4.7 Mb de novo 12q15‐q21.1 microdeletion in a patient with FHS and intellectual deficiency. Pangenomic 244K array‐CGH performed in a series of 12 patients with FHS failed to identify overlapping deletions. We hypothesized that FHS is caused by haploinsufficiency of one of the 19 genes or predictions located in the deletion found in our index patient. Since none... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590889 Fri, 13 Jan 2012 05:00:00 +0100 5590889 http://www.medworm.com/index.php?rid=5590888&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34403 We report on an 8‐year‐old boy with striking right hemihypoplasia, resulting in limb asymmetry and fixed dislocation of right hip. Skin on the affected side showed three distinct nevi: (i) A whorled, hairless nevus of the scalp in close proximity with (ii) epidermal hyperpigmentation following lines of Blaschko on the neck and right upper limb, and (iii) multiple telangiectatic nevi of the right lower limb and hemiscrotum. Didymosis atricho‐melanotica was proposed for the combination of adjacent patchy congenital alopecia and linear hyperpigmentation, while phacomatosis atricho‐pigmento‐vascularis appears to define the entire cutaneous phenotype, thus implying the involvement of three neighboring loci influencing the development of distinct constituents of the skin. Given the str... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590888 Fri, 13 Jan 2012 05:00:00 +0100 5590888 http://www.medworm.com/index.php?rid=5590887&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34404 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590887 Fri, 13 Jan 2012 05:00:00 +0100 5590887 http://www.medworm.com/index.php?rid=5590886&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34406 AbstractFibrochondrogenesis is a severe, recessively inherited skeletal dysplasia shown to result from mutations in the gene encoding the proα1(XI) chain of type XI collagen, COL11A1. The first of two cases reported here was the affected offspring of first cousins and sequence analysis excluded mutations in COL11A1. Consequently, whole‐genome SNP genotyping was performed to identify blocks of homozygosity, identical‐by‐descent, wherein the disease locus would reside. COL11A1 was not within a region of homozygosity, further excluding it as the disease locus, but the gene encoding the proα2(XI) chain of type XI collagen, COL11A2, was located within a large region of homozygosity. Sequence analysis identified homozygosity for a splice donor mutation in intron 18. Exon trapping demonst... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590886 Fri, 13 Jan 2012 05:00:00 +0100 5590886 http://www.medworm.com/index.php?rid=5590885&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34407 AbstractMutations in the CLDN14 gene are known to cause autosomal recessive (AR) non‐sydromic hearing loss (NSHL) at the DFNB29 locus on chromosome 21q22.13. As part of an ongoing study to localize and identify NSHL genes, the ARNSHL segregating in four Pakistani consanguineous families were mapped to the 21q22.13 region with either established or suggestive linkage. Given the known involvement of CLDN14 gene in NSHL, DNA samples from hearing‐impaired members from the four families were sequenced to potentially identify causal variants within this gene. Three novel CLDN14 mutations, c.167G>A (p.Trp56*), c.242G>A (p.Arg81His), and c.694G>A (p.Gly232Arg), segregate with hearing loss (HL) in three of the families. The previously reported CLDN14 mutation c.254T>A (p.Val85Asp) w... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590885 Fri, 13 Jan 2012 05:00:00 +0100 5590885 http://www.medworm.com/index.php?rid=5590884&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34415 AbstractMucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X‐linked lysosomal storage disease caused by a deficiency of iduronate‐2‐sulfatase (IDS). Two affected girls with moderate and severe forms of MPS II with normal karyotypes and increased urinary dermatan sulphate and heparin sulphate excretion and marked deficiencies of IDS activity are reported. Molecular studies showed that case 1 has a heterozygous mutation c.1568A > G (p.Y523C) associated with almost totally skewed inactivation of the normal maternal X chromosome, and case 2 has a heterozygous deletion that includes exons 1–4 of IDS (minimal deletion range c.1–103_184del). The multi‐exon deletion correlated with early onset of the disease and severe phenotype with intellectual disability, whereas t... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590884 Fri, 13 Jan 2012 05:00:00 +0100 5590884 http://www.medworm.com/index.php?rid=5590883&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34421 AbstractNevoid basal cell carcinoma syndrome (NBCCS) is characterized by developmental defects and tumorigenesis. The clinical manifestations of NBCCS have been reported in large epidemiological studies from the United States, the United Kingdom, and Australia, but not from an Asian country. We conducted a nationwide survey and identified 311 NBCCS patients in Japan. We investigated the detailed clinical manifestations of 157 patients ranging in age from 9 months to 77 years old (mean: 33.1 years). We then compared the frequency and age of onset for various tumors developed in Japanese NBCCS patients with patients from the three countries listed above in which NBCCS studies were previously conducted. Our most significant finding was the low frequency of basal cell carcinoma (BCC) in Japane... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590883 Fri, 13 Jan 2012 05:00:00 +0100 5590883 http://www.medworm.com/index.php?rid=5590882&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34422 This study tested a web‐based tutorial to assess its effectiveness in improving physicians' perceived comfort with both ambiguous and more medically factual situations as they deliver diagnoses of DS. Based on this web tutorial that integrated prenatal and postnatal information into virtual patient scenarios, the study assessed pediatrics residents' knowledge and comfort in delivering a diagnosis of DS pre and postnatally. A separate survey, given at the same time, asked for residents' perception of their need for this training. Ninety‐one volunteer residents from 10 pediatric training programs across the country participated. The tutorial yielded significant improvement in knowledge and a significant decrease in perceived level of discomfort in both ambiguous situations and more medic... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590882 Fri, 13 Jan 2012 05:00:00 +0100 5590882 http://www.medworm.com/index.php?rid=5590881&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34427 We describe a 14‐year‐old boy with an 8.97 Mb deletion of 2p23.3–24.3 detected by array comparative genomic hybridization (array CGH) who had intellectual disability (ID), unusual facial features, cryptorchidism, skeletal myopathy, dilated cardiomyopathy (DCM), and postnatal overgrowth (macrocephaly and tall stature). We compared the clinical features of the present case to previously described patients with an interstitial deletion within this chromosomal region and conclude that our patient exhibits a markedly different phenotype. Additional patients are needed to further delineate phenotype–genotype correlations © 2012 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590881 Fri, 13 Jan 2012 05:00:00 +0100 5590881 http://www.medworm.com/index.php?rid=5590880&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34428 AbstractWe identified a novel missense mutation, c.424G>C (p.Val142Leu) in PRPS1 in a patient with uric acid overproduction without gout but with developmental delay, hypotonia, hearing loss, and recurrent respiratory infections. The uric acid overproduction accompanying this combination of symptoms suggests that the patient presented with phosphoribosylpyrophosphate (PRPP) synthetase superactivity, but recurrent infections have not been associated with superactivity until now. However, recurrent infections are a prominent feature of patients with Arts syndrome, which is caused by PRPS1 loss‐of‐function mutations, indicating that the patient reported here has an intermediate phenotype. Molecular modeling predicts that the p.Val142Leu change affects both allosteric sites that are inv... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590880 Fri, 13 Jan 2012 05:00:00 +0100 5590880 http://www.medworm.com/index.php?rid=5590879&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34272 We report on the fifth case, and oldest reported patient, of an individual affected with mosaic tetrasomy 5p resulting from an isochromosome 5p [i(5)(p10)] marker chromosome. A syndrome of mosaic tetrasomy 5p is defined, and includes the following features seen in the reported cases: developmental delay, seizures, ventriculomegaly (other brain anomalies), small stature/growth delay and mosaic pigmentary skin changes. Other findings include various dysmorphic facial features as well as hand and foot anomalies. This syndrome is likely more common than suggested in the literature, as the clinical presentation can be variable, and the chromosome anomaly is unlikely to be found on routine karyotype of peripheral blood lymphocytes. The i(5)(p10) marker chromosome is found only as a mosaic anomal... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590879 Fri, 13 Jan 2012 05:00:00 +0100 5590879 http://www.medworm.com/index.php?rid=5590878&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34412 We report on a patient initially diagnosed with SRS carrying a segmental maternal UPD of chromosome 7 [upd(7q)mat]. By further screening the patient's DNA for methylation defects on other chromosomes we identified a hypomethylation of the paternally methylated DLK1/GTL2 locus in 14q32, an epigenotype typically associated with the upd(14)mat phenotype. Detailed clinical analysis confirmed the molecular finding in the patient indicating that the 14q32 epimutation was clinically preponderant. The parallel occurrence of upd(7q)mat and a DLK1/GTL2 hypomethylation in the same patient is a unique finding. Indeed, both disturbances might have occurred coincidentally, but it can also be hypothesized that the upd(7q)mat as the initial genomic mutation represents a trans‐acting mutation causing an ... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590878 Fri, 13 Jan 2012 05:00:00 +0100 5590878 http://www.medworm.com/index.php?rid=5567099&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34402 AbstractThe macrocephaly‐capillary malformation syndrome (M‐CM), which we here propose to rename the megalencephaly‐capillary malformation syndrome (MCAP; alternatively the megalencephaly‐capillary malformation‐polymicrogyria syndrome), and the more recently described megalencephaly‐polymicrogyria‐polydactyly‐hydrocephalus syndrome (MPPH) are two megalencephaly (MEG) disorders that involve a unique constellation of physical and neuroimaging anomalies. We compare the features in 42 patients evaluated for physical and neuroimaging characteristics of MCAP and MPPH and propose a more global view of these syndromes based on classes of developmental abnormalities that include primary MEG and growth dysregulation, developmental vascular anomalies (primarily capillary malformations... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5567099 Fri, 06 Jan 2012 05:00:00 +0100 5567099 http://www.medworm.com/index.php?rid=5590877&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34423 We report on anthropometric charts of infants with these conditions using data from the Vermont Oxford Network (VON). Data from a total of 5,147 infants with T21 aged 22–41 weeks, 1,053 infants with T18 aged 22–41 weeks, and 613 infants with T13 aged 22–40 weeks were used to create birth weight for GA charts. Head circumference for GA charts were created for infants with T21 only. Combined‐sex charts were generated for infants with T18 or T13 while sex‐specific charts were generated for infants with T21. Smoothed centiles were created using LmsChartMaker Pro 2.3. Among the three examined groups, infants with T18 were the most likely to be growth restricted while infants with T21 were the least likely to be growth restricted. The new charts for infants with T21 were also compared ... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5590877 Sun, 01 Jan 2012 05:00:00 +0100 5590877 http://www.medworm.com/index.php?rid=5567098&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34429 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5567098 Sun, 01 Jan 2012 05:00:00 +0100 5567098 http://www.medworm.com/index.php?rid=5531287&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34312 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531287 Fri, 23 Dec 2011 03:29:07 +0100 5531287 http://www.medworm.com/index.php?rid=5531286&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34323 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531286 Fri, 23 Dec 2011 03:29:05 +0100 5531286 http://www.medworm.com/index.php?rid=5531285&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35200 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531285 Fri, 23 Dec 2011 03:28:15 +0100 5531285 http://www.medworm.com/index.php?rid=5531284&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35199 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531284 Fri, 23 Dec 2011 03:28:13 +0100 5531284 http://www.medworm.com/index.php?rid=5531283&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35198 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531283 Fri, 23 Dec 2011 03:28:12 +0100 5531283 http://www.medworm.com/index.php?rid=5531282&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35219 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531282 Fri, 23 Dec 2011 03:28:11 +0100 5531282 http://www.medworm.com/index.php?rid=5531281&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.35218 AbstractPhotogrpahic display of the different degrees of microtia accompanied by a normal external ear on the upper left figure. See article by Luquetti et al. in this issue. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531281 Fri, 23 Dec 2011 03:28:10 +0100 5531281 http://www.medworm.com/index.php?rid=5531278&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34418 AbstractRett syndrome (RTT; OMIM 312750) is an X‐linked dominant neurodevelopmental disorder leading to cognitive and motor impairment, epilepsy, and autonomic dysfunction in females. Since the discovery that RTT is caused by mutations in MECP2, large retrospective genotype–phenotype correlation studies have been performed. A number of general genotype–phenotype relationships were confirmed and specific disorder profiles were described. Nevertheless, conflicting results are still under discussion, partly due to the variability in classification of mutations, assessment tools, and structure of the data sets. The aim of this study was to investigate relationships between genotype and specific clinical data collected by the same experienced physician in a well‐documented RTT cohort, a... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531278 Fri, 23 Dec 2011 03:27:48 +0100 5531278 http://www.medworm.com/index.php?rid=5531280&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34216 We present 10 previously unreported individuals with 9q22.3 deletions that include PTCH1. While 7 of the 10 patients (7 females, 3 males) did not meet strict clinical criteria for BCNS at the time of molecular diagnosis, almost all of the patients were too young to exhibit many of the diagnostic features. A number of the patients exhibited metopic craniosynostosis, severe obstructive hydrocephalus, and macrosomia, which are not typically observed in BCNS. All individuals older than a few months of age also had developmental delays and/or intellectual disability. Only facial features typical of BCNS, except in those with prominent midforeheads secondary to metopic craniosynostosis, were shared among the 10 patients. The deletions in these individuals ranged from 352 kb to 20.5 Mb in siz... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531280 Wed, 21 Dec 2011 05:00:00 +0100 5531280 http://www.medworm.com/index.php?rid=5531279&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34250 AbstractDeletion of chromosome 22q11.2 is considered one of the most frequent genetic causes of cardiovascular malformations. It is frequently associated with conotruncal malformations, but may also be present among patients with nonconotruncal malformations. The aim of the present study was to establish the prevalence of the 22q11.2 deletion in an unselected population‐based cohort of children with various cardiovascular malformations. The study population was defined as children born in 2000–2008 who were registered in the Danish National Patient Registry with a diagnosis of cardiovascular malformation from one of the two national departments of pediatric cardiology. Sensitive multiplex ligation‐dependent probe amplification was performed on dried blood spot samples from each indiv... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5531279 Wed, 21 Dec 2011 05:00:00 +0100 5531279 http://www.medworm.com/index.php?rid=5481671&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34222 We report on clinical and cytogenetic studies in a 7‐year‐old child with moderate intellectual disability, short stature, mild dysmorphism, and hearing loss. R‐chromosome banding showed a de novo autosomal marker originating from the 17p chromosome segment in all cells analyzed. Array comparative genome hybridization (aCGH) was used to determine the gene content and proximal and distal breakpoints of the small supernumerary marker chromosome (SMC). These breakpoints mapped to the centromere of chromosome 17 and the 17p11.2 region, respectively. Unexpectedly, aCGH analysis also revealed a de novo deletion of 800 kb encompassing six genes in the 17q23.2 region, including MED13 (also known as THRAP1). We compared our patient with other reported cases of SMC(17), to determine the respe... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5481671 Wed, 07 Dec 2011 05:00:00 +0100 5481671 http://www.medworm.com/index.php?rid=5481670&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34374 This article reports on the first psychometric validation of the English translation of the PPC scale. Previous research has shown that the Hebrew and Dutch translations have good psychometric properties. However, the psychometric properties of the English translation have not been tested, and there is disagreement about the factor structure, with implications for how to score the measure. A total of 395 patients attending a clinical genetics appointment in the United Kingdom completed several measures at baseline, and a further 241 also completed measures at 2–4 weeks follow‐up. The English language PPC has (a) a one‐factor structure, (b) convergent validity with internal health locus of control (IHLC), satisfaction with life (SWL), depression, and authenticity, (c) high internal co... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5481670 Wed, 07 Dec 2011 05:00:00 +0100 5481670 http://www.medworm.com/index.php?rid=5481673&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34372 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5481673 Tue, 06 Dec 2011 05:00:00 +0100 5481673 http://www.medworm.com/index.php?rid=5481672&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34391 AbstractHearing loss is the most prevalent sensory perception deficit in humans, affecting 1/500 newborns, can be syndromic or nonsyndromic and is genetically heterogeneous. Nearly 80% of inherited nonsyndromic bilateral sensorineural hearing loss (NBSNHI) is autosomal recessive. Although many causal genes have been identified, most are minor contributors, except for GJB2, which accounts for nearly 50% of all recessive cases of severe to profound congenital NBSNHI in some populations. More than 60% of children with a NBSNHI do not have an identifiable genetic cause. To identify genetic contributors, we genotyped 659 GJB2 mutation negative pediatric probands with NBSNHI and assayed for copy number variants (CNVs). After identifying 8 mild‐moderate NBSNHI probands with a Chr15q15.3 deletio... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5481672 Tue, 06 Dec 2011 05:00:00 +0100 5481672 http://www.medworm.com/index.php?rid=5472847&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34385 This article is a U.S. Government work and is in the public domain in the USA. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472847 Fri, 02 Dec 2011 05:00:00 +0100 5472847 http://www.medworm.com/index.php?rid=5472846&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34377 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472846 Fri, 02 Dec 2011 05:00:00 +0100 5472846 http://www.medworm.com/index.php?rid=5472845&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34383 This study is a large, multisite, population‐based study of nonsyndromic birth defects. Prevalence estimates were obtained using data from spina bifida cases (live births, fetal deaths, and elective terminations) and total live births in the study regions. From October 1997 through December 2005, 1,046 infants/fetuses with spina bifida were delivered, yielding a prevalence of 3.06 per 10,000 live births. Differences in the prevalences of SBM vs. SBL, isolated versus non‐isolated SBM, and lesion level in isolated SBM among case offspring were observed by maternal race/ethnicity. Compared to non‐Hispanic (NH) White mothers, offspring of Hispanic mothers had higher prevalences of each subtype and most sub‐phenotypes, while offspring of NH Black mothers generally had lower prevalences.... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472845 Fri, 02 Dec 2011 05:00:00 +0100 5472845 http://www.medworm.com/index.php?rid=5472844&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34384 AbstractCornelia de Lange syndrome is a pleiotropic developmental syndrome characterized by growth and cognitive impairment, facial dysmorphic features, limb anomalies, and other malformations. Mutations in core cohesin genes SMC1A and SMC3, and the cohesin regulatory gene, NIPBL, have been identified in Cornelia de Lange syndrome probands. Patients with NIPBL mutations have more severe phenotypes when compared to those with mutations in SMC1A or SMC3. To date, 26 distinct SMC1A mutations have been identified in patients with Cornelia de Lange syndrome. Here, we describe a 3‐year‐old girl with psychomotor and cognitive impairment, mild facial dysmorphic features but no limb anomaly, heterozygous for a c.1487G>A mutation in SMC1A which predicts p.Arg496His. We show that this mutation... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472844 Fri, 02 Dec 2011 05:00:00 +0100 5472844 http://www.medworm.com/index.php?rid=5472843&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34386 AbstractIn the nearly quarter‐century since the first international symposium on Marfan syndrome, enormous progress has been achieved in clinical, translational, and basic research. The 8th symposium, at the end of 2010, provides a useful summary of the current status of investigations, reveals why life‐expectancy has improved so markedly during the past 30 years, and lays out a clear path for future endeavors, not only in Marfan syndrome, but in the expanding array of conditions related either through phenotype or pathogenesis. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472843 Fri, 02 Dec 2011 05:00:00 +0100 5472843 http://www.medworm.com/index.php?rid=5472842&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34367 AbstractRett syndrome (RTT) is a rare neurodevelopmental disorder, linked to MECP2 gene mutations in the majority of cases, which results in severe disability and is associated with several comorbidities. The clinical condition of RTT patients tends to stabilize over time, and prolonged survival has recently been demonstrated. However, limited information is available on the long‐term course of older patients with RTT, especially among those in Southern Europe. The aim of our study is to evaluate the main clinical features and state of health of adult Italian patients with RTT and to present their evolution over time, identifying major clinical issues present at different ages. A total of 130 families of patients with RTT aged ≥14 years were asked to complete a questionnaire, 84 of whi... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472842 Fri, 02 Dec 2011 05:00:00 +0100 5472842 http://www.medworm.com/index.php?rid=5472841&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34368 AbstractFamilial hypercholesterolemia (FH) is an autosomal dominant disorder with a high risk of coronary heart disease at a young age that can be reduced by cholesterol‐lowering drugs. Computer simulation was used to estimate the screening performance of three strategies of cascade testing for FH (a process of searching for relatives with FH once an individual is diagnosed with FH): (i) testing parents, siblings, and children (1st degree relatives) of an FH index case, (ii) testing (i) and testing 1st degree relatives of subsequently identified relatives with FH, and (iii) testing (ii) and also testing aunts, uncles, nephews, nieces, grandparents, and first cousins (2nd or 3rd degree relatives) when 1st degree relatives of an individual with FH are not available. For cascade testing to ... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472841 Fri, 02 Dec 2011 05:00:00 +0100 5472841 http://www.medworm.com/index.php?rid=5472840&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34388 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472840 Fri, 02 Dec 2011 05:00:00 +0100 5472840 http://www.medworm.com/index.php?rid=5472839&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34389 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472839 Fri, 02 Dec 2011 05:00:00 +0100 5472839 http://www.medworm.com/index.php?rid=5472838&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34390 We report on a boy born to consanguineous parents, who had hypertelorism, a broad nasal bridge, ridge and tip, bifid nasal tip, cleft alae nasi, broad columella, unilateral preauricular tag, shallow labiogingival sulcus, and bilateral large parietal foramina. Cranial MRI revealed a kinked corpus body and small cerebellar vermis. Molecular analysis uncovered a homozygous c.673C > G (p.Q225E) mutation in ALX4 gene. We compare the relatively mild phenotype in the patient to the more marked phenotype described in other patients with homozygous ALX4 mutations, and to the phenotypes in patients with mutations in other ALX genes. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472838 Fri, 02 Dec 2011 05:00:00 +0100 5472838 http://www.medworm.com/index.php?rid=5472837&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34393 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472837 Fri, 02 Dec 2011 05:00:00 +0100 5472837 http://www.medworm.com/index.php?rid=5472836&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34394 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472836 Fri, 02 Dec 2011 05:00:00 +0100 5472836 http://www.medworm.com/index.php?rid=5472835&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34395 We report on a 13‐year‐old boy with this syndrome manifesting childhood myelodysplastic syndrome (MDS). He had characteristic facial features, hypospadias, and mild developmental delay. He showed neutropenia and thrombocytopenia for several years. At age 13 years, bone marrow examination was performed, which showed a sign suggestive of childhood MDS: mild dysplasia in the myeloid, erythroid, and megakaryocytic cell lineages. Array comparative genomic hybridization (array CGH) revealed a de novo 3.4 Mb 15q24.1q24.3 deletion. Although MDS has not been described in patients with the syndrome, a boy was reported to have acute lymphoblastic leukemia (ALL). The development of MDS and hematological malignancy in the syndrome might be caused by the haploinsufficiency of deleted 15q24 segment... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472835 Fri, 02 Dec 2011 05:00:00 +0100 5472835 http://www.medworm.com/index.php?rid=5472834&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34387 In conclusion, the phenotypic spectrum of microdeletions in 16q12 is broad and comprises variable degrees of psychomotor delay and intellectual disability, craniofacial anomalies, and additional features, including heart defects, brain malformations, and limb anomalies. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472834 Fri, 02 Dec 2011 05:00:00 +0100 5472834 http://www.medworm.com/index.php?rid=5472833&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34396 We describe a newborn girl with multiple congenital anomalies and abnormal phenotype comprising underdeveloped corpus callosum with ventriculomegaly, chorioretinal atrophy, pulmonary arterial hypertension, annular pancreas, horseshoe kidney, asymmetric limb and chest anomalies, spinal segmentation defects, hypertrichosis, and unusual face with large anterior fontanel, high anterior hairline, broad forehead, mildly underdeveloped midface, hypertelorism, depressed nasal bridge, short and upturned nose, large mouth, retrognathia, and large and malformed ears. Work‐up included cytogenetic studies of lymphocytes and skin fibroblasts, subtelomere Multiplex Ligation‐dependent Probe Amplification (MLPA), whole‐genome oligo‐array, and molecular analysis of SETBP1 and NSDHL: no abnormalities... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472833 Fri, 02 Dec 2011 05:00:00 +0100 5472833 http://www.medworm.com/index.php?rid=5472832&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34397 We report on a mother and daughter with a 12q14 microdeletion. To our knowledge these are the first reported familial cases with the syndrome. We also discuss the genes in the deleted area that may be contributing to the phenotype. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472832 Fri, 02 Dec 2011 05:00:00 +0100 5472832 http://www.medworm.com/index.php?rid=5472831&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34398 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472831 Fri, 02 Dec 2011 05:00:00 +0100 5472831 http://www.medworm.com/index.php?rid=5472830&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34399 AbstractThe availability of tests to detect genetic conditions prenatally has expanded considerably in recent decades. These advances allow women and couples choices; the choice of whether or not to undergo prenatal screening or diagnosis and therefore the choice whether to continue or terminate a pregnancy. Following prenatal testing many people choose to terminate an affected pregnancy, however little is known about the experiences of parents who choose to continue such a pregnancy. This exploratory qualitative study involved in‐depth interviews with five mothers and four fathers who experienced a pregnancy where a genetic diagnosis was, or could have been, detected prenatally. Transcripts of the interviews were analyzed using thematic analysis. While the participants' experiences of g... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472830 Fri, 02 Dec 2011 05:00:00 +0100 5472830 http://www.medworm.com/index.php?rid=5472829&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34359 AbstractNeurofibromatosis type 2 (NF2) is a tumor suppressor syndrome characterized by bilateral vestibular schwannomas (VS) which often result in deafness despite aggressive management. Meningiomas, ependymomas, and other cranial nerve and peripheral schwannomas are also commonly found in NF2 and collectively lead to major neurologic morbidity and mortality. Traditionally, the overall survival rate in patients with NF2 is estimated to be 38% at 20 years from diagnosis. Hence, there is a desperate need for new, effective therapies. Recent progress in understanding the molecular basis of NF2 related tumors has aided in the identification of potential therapeutic targets and emerging clinical therapies. In June 2010, representatives of the international NF2 research and clinical community co... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472829 Fri, 02 Dec 2011 05:00:00 +0100 5472829 http://www.medworm.com/index.php?rid=5510705&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34410 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5510705 Thu, 01 Dec 2011 05:00:00 +0100 5510705 http://www.medworm.com/index.php?rid=5481669&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34392 AbstractRecently, a revised Ghent nosology has been established for the diagnosis of Marfan syndrome (MFS) that puts more weight on the aortic root aneurysm and ectopia lentis. We compared the application of the Ghent and revised Ghent nosologies in adult Korean patients for whom there is suspicion of MFS. From January 1995 to June 2010, we enrolled 106 patients older than 20 years for whom there was suspicion of MFS, and who had undergone genetic analysis of the fibrillin‐1 gene (FBN1). Of 106 patients, 86 patients (81%) fulfilled the criteria of the Ghent nosology, and 84 patients (79%) met the criteria of the revised Ghent nosology. The two patients who met the Ghent nosology criteria, but not the criteria of the revised Ghent nosology were diagnosed with Loeys–Dietz syndrome and MA... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5481669 Thu, 01 Dec 2011 05:00:00 +0100 5481669 http://www.medworm.com/index.php?rid=5472828&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34382 AbstractA woman with psychomotor developmental delay, congenital glaucoma, and distinctive facial features, and a short neck was diagnosed with Jacobsen syndrome (JBS) at age 40 years. A previously reported balanced translocation between chromosome 11 and 22 instead showed an unbalanced translocation by a microarray‐based comparative hybridization analysis with the final karyotype of 46,XX,der(11)t(11;22)(q23.3;q11.21),del(22)(q11.21) dn. The breakpoint of chromosome 11 was determined to be at TECTA and not near the apolipoprotein gene cluster site or the fragile site (FRA11B), which are commonly seen in patients with t(11;22) and patients with typical 11q deletions, respectively. Although the phenotypic features of the patient, including psychomotor developmental delay, distinctive feat... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5472828 Thu, 01 Dec 2011 05:00:00 +0100 5472828 http://www.medworm.com/index.php?rid=5436176&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34243 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436176 Wed, 23 Nov 2011 02:41:44 +0100 5436176 http://www.medworm.com/index.php?rid=5436175&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34381 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436175 Wed, 23 Nov 2011 02:40:38 +0100 5436175 http://www.medworm.com/index.php?rid=5436174&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34380 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436174 Wed, 23 Nov 2011 02:40:37 +0100 5436174 http://www.medworm.com/index.php?rid=5436173&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34379 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436173 Wed, 23 Nov 2011 02:40:36 +0100 5436173 http://www.medworm.com/index.php?rid=5436172&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34409 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436172 Wed, 23 Nov 2011 02:40:35 +0100 5436172 http://www.medworm.com/index.php?rid=5436171&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34408 AbstractSagittal MIP (maximum intensity projection) image (a), 3D VR (volume rendering) image (b), demonstrating the irregular dissection flap and thrombosed false lumen of the left internal carotid artery. The arrows highlight the arterial lesion on both images, respectively. See article by Mortani Barbosa et al. in this issue. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436171 Wed, 23 Nov 2011 02:40:34 +0100 5436171 http://www.medworm.com/index.php?rid=5436148&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34370 AbstractPoland anomaly (PA) is a pectoral muscle hypoplasia/aplasia variably associated with ipsilateral thoracic (TA) and/or upper limb anomalies (ULA). PA is usually sporadic and sometimes familial, making recurrence risk an issue in genetic counseling. Multidisciplinary evaluation of 240 PA patients was carried out, including physical examination of patients and their parents in 190 PA (subjects of the study). Familial conditions were classified into three groups. Group1: true familial PA (F‐PA): pectoral muscle defects with familial recurrence: 8(4.2%). Group2: familial Poland‐like anomaly families (F‐PLA): PA index case and ≥1 relative(s) showing normal pectoral muscles but ULA and/or TA common in PA: 16(8.4%). Group3: sporadic PA (S‐PA): 166(87.4%). F‐PA indicated a stron... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436148 Wed, 23 Nov 2011 02:39:59 +0100 5436148 http://www.medworm.com/index.php?rid=5436170&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34354 We report on clinical findings for two new individuals with a submicroscopic deletion of FOXP2: a boy with severe apraxia of speech and his currently moderately affected mother. A 1.57 Mb deletion on chromosome 7q31 was detected by array comparative genomic hybridization (aCGH). In addition to FOXP2, the patients' deletion involves two other genes, MDFIC and PPP1R3A, neither of which has been associated with speech or language disorders. Thus, findings for these two family members provide informative phenotypic information on FOXP2 haploinsufficiency. Evaluation by a clinical geneticist indicated no major congenital anomalies or dysmorphic features. Evaluations by a clinical psychologist and occupational therapist indicated cognitive‐linguistic processing and sensorimotor control defic... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436170 Mon, 21 Nov 2011 05:00:00 +0100 5436170 http://www.medworm.com/index.php?rid=5436169&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34355 We report on a newborn who presented with prolonged QT interval and associated polymorphic ventricular tachycardia, dysmorphic facial features, syndactyly of the hands and feet, and joint contractures, suggestive of TS. He developed a stroke, subsequent intractable seizures, and was found to have cortical blindness and later profound developmental delay. Initial targeted mutation analysis did not identify either of the previously described TS associated mutations; however, full gene sequencing detected a novel CACNA1C gene mutation (p.Ala1473Gly). The clinical and genetic findings in our case expand both the clinical and molecular knowledge of TS. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436169 Mon, 21 Nov 2011 05:00:00 +0100 5436169 http://www.medworm.com/index.php?rid=5436168&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34358 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436168 Mon, 21 Nov 2011 05:00:00 +0100 5436168 http://www.medworm.com/index.php?rid=5436167&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34308 We report a patient with a 47,XYY karyotype and submicroscopic terminal 6p deletion. Further characterization of the deletion with array comparative genome hybridization also revealed a cryptic microduplication on chromosome 19. The patient showed dysmorphic features, neuromotor retardation, and profound language impairment, in absence of hearing loss and structural eye anomalies. As far as we know this is the first reported terminal 6p25.1 deletion case without eye dysgenesis precisely characterized by array‐CGH. Our result suggests that the genes in this region may not be obvious candidates for hearing loss and demonstrate the need for further elucidation of the function of the genes involved in eye developmental processes. © 2011 Wiley Periodicals, Inc. (Source: American Journal of M... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436167 Mon, 21 Nov 2011 05:00:00 +0100 5436167 http://www.medworm.com/index.php?rid=5436166&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34337 In this report we describe a new simplex case and a previously unreported family with affected individuals in three generations documenting clinical variability. Linkage study for markers located in candidate region for ACS1 (1p21.1–q23.3) was excluded in our familial case, reinforcing the hypothesis of genetic heterogeneity for this condition. A review of the literature focusing diagnostic criteria and features of ACS was performed. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436166 Mon, 21 Nov 2011 05:00:00 +0100 5436166 http://www.medworm.com/index.php?rid=5436165&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34343 In conclusion, the prevalence of OC live births varies significantly in the Netherlands, not only between but also within registries. This underlines that extrapolation of regional cleft data should be done with caution. To further investigate OC etiology and evaluate preventive strategies, future studies should consider geographical differences—between and within countries—regarding the various cleft sub‐phenotypes among live births, stillbirths, and pregnancy terminations. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436165 Mon, 21 Nov 2011 05:00:00 +0100 5436165 http://www.medworm.com/index.php?rid=5436164&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34347 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436164 Mon, 21 Nov 2011 05:00:00 +0100 5436164 http://www.medworm.com/index.php?rid=5436163&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34349 AbstractNeuroligin 1 (NLGN1) is one of five members of the neuroligin gene family and may represent a candidate gene for neurological disorders, as members of this family are involved in formation and remodeling of central nervous system synapses. NLGN1 is expressed predominantly in the central nervous system, where it dimerizes and then binds with β‐neurexin to form a functional synapse. Mutations in neurexin 1 (NRXN1) as well as two other members of the neuroligin family, NLGN3 and NLGN4, have been associated with autism and mutations in NLGN4 have also been associated with intellectual disability, seizures, and EEG abnormalities. Genomic microarray is recommended for the detection of chromosomal gains or losses in patients with intellectual disability and multiple congenital anomalie... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436163 Mon, 21 Nov 2011 05:00:00 +0100 5436163 http://www.medworm.com/index.php?rid=5436162&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34350 We report here on a patient with a mild holoprosencephaly spectrum phenotype (bilateral cleft lip and palate and abnormal pituitary gland formation with panhypopituitarism) and normal psychomotor development, who was found to carry a 1.3 Mb submicroscopic heterozygous deletion in 2q14.2, encompassing the GLI2 gene. We review the genotype and phenotype of previously published probands with GLI2 aberrations. Our findings confirm the association of haploinsufficiency of GLI2 and mild HPE spectrum features. Consistent with prior reports, we observed incomplete penetrance of the deletion in the family, illustrating the multifactorial etiology of holoprosencephaly spectrum features. In addition to the holoprosencephaly spectrum features, the proband had heterotaxy of the abdominal organs. Muta... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436162 Mon, 21 Nov 2011 05:00:00 +0100 5436162 http://www.medworm.com/index.php?rid=5436161&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34351 AbstractRett syndrome is a rare neurological disorder affecting girls and usually caused by a mutation on the MECP2 gene. It is estimated that approximately 1,000 girls are born every year in China with Rett syndrome but far fewer have received a diagnosis. Fourteen of 74 Chinese families known to the International Rett Syndrome Phenotype Database participated in this qualitative study. Telephone interviews were conducted in Mandarin to explore pathways to a diagnosis of Rett syndrome in China and associated barriers. Families consulted multiple clinical centers and eventually received a diagnosis at a centrally located hospital. Over the course of this pathway, families encountered lack of knowledge and diagnostic expertise for Rett syndrome at local levels and a heavily over‐burdened h... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436161 Mon, 21 Nov 2011 05:00:00 +0100 5436161 http://www.medworm.com/index.php?rid=5436160&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34352 AbstractMicrotia is a congenital anomaly of the ear that ranges in severity from mild structural abnormalities to complete absence of the ear, and can occur as an isolated birth defect or as part of a spectrum of anomalies or a syndrome. Microtia is often associated with hearing loss and patients typically require treatment for hearing impairment and surgical ear reconstruction. The reported prevalence varies among regions, from 0.83 to 17.4 per 10,000 births, and the prevalence is considered to be higher in Hispanics, Asians, Native Americans, and Andeans. The etiology of microtia and the cause of this wide variability in prevalence are poorly understood. Strong evidence supports the role of environmental and genetic causes for microtia. Although some studies have identified candidate gen... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436160 Mon, 21 Nov 2011 05:00:00 +0100 5436160 http://www.medworm.com/index.php?rid=5436159&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34360 We report on a female with monosomy X mosaicism and a phenotype suggestive of a severe form of CdLS who presented with growth and mental retardation, multiple congenital anomalies, and facial dysmorphism. Array CGH confirmed mosaic monosomy X and identified a novel deletion of SMC1A spanning multiple exons, suggesting a possible loss‐of‐function effect. Sequencing of both genomic and cDNA demonstrated an 8,152 bp deletion of genomic DNA from exon 13 to intron 16. Although a loss‐of‐function effect cannot be excluded, the resulting mRNA remains in‐frame and is expressed in peripheral blood lymphocytes, suggesting a dominant‐negative effect. We hypothesize that the size of this deletion compared to previously reported mutations may account for this patient's severe CdLS phenoty... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436159 Mon, 21 Nov 2011 05:00:00 +0100 5436159 http://www.medworm.com/index.php?rid=5436158&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34361 AbstractIn April 2011, the American Congress of Obstetricians and Gynecologists (formerly the American College of Obstetrics and Gynecology [ACOG]), updated its policy on carrier screening for cystic fibrosis and proposed that because of the increasing difficulty in assigning a single ethnicity to individuals, “It is reasonable, therefore to offer CF carrier screening to all patients.” However, ACOG continues to use ethnicity in its guidelines about carrier testing for autosomal recessive disorders like sickle cell disease (SCD) and Tay‐Sachs disease (TSD). This practice is in marked contrast with newborn screening (NBS) which is universally provided for all conditions. In this manuscript, I evaluate the discrepant role of ethnicity in NBS and carrier screening. I argue that ACOG nee... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436158 Mon, 21 Nov 2011 05:00:00 +0100 5436158 http://www.medworm.com/index.php?rid=5436157&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34362 AbstractThe rise in the rate of multiple births since the 1980s is due to the effect of advanced maternal age and increased use of assisted reproductive technology (ART). To determine the trends of prevalence in twin births, we studied the data of a population‐based birth defects monitoring system during 26 years in Kanagawa Prefecture, Japan. A total of 15,380 twins from 7,690 deliveries were ascertained from 990,978 births in the Kanagawa Birth Defects Monitoring Program (KAMP) during 1981–2008. From the start of KAMP in 1981, the incidence of twin births had been consistently increasing from 57.0 to 98.6 per 10,000 deliveries until 2003, but after this time, the incidence declined to 78.5 in 2007. While the rate of monozygotic twins has been stable (∼40 per 10,000 deliveries) afte... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436157 Mon, 21 Nov 2011 05:00:00 +0100 5436157 http://www.medworm.com/index.php?rid=5436156&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34363 We report on a female patient with early infantile epileptic encephalopathy and severe psychomotor disability possessing a de novo balanced translocation t(1;9)(q32;q13). The patient showed clonic convulsions of extremities 2 days after birth. Electroencephalogram (EEG) transiently showed atypical suppression‐burst pattern. The seizures evolved to brief tonic spasms, and hypsarrhythmia on EEG was noticed at age of 5 months, indicating the transition to West syndrome. By using fluorescent in situ hybridization (FISH), southern hybridization, and inverse PCR, the translocation breakpoints were successfully determined at the nucleotide level. The 1q32.1 breakpoint was located within a segmental duplication and disrupted the gene encoding Slit‐Robo Rho GTPase activating protein 2 (SRGAP2).... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436156 Mon, 21 Nov 2011 05:00:00 +0100 5436156 http://www.medworm.com/index.php?rid=5436155&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34364 AbstractIndividuals with pericentric inversions are at risk for producing offspring with chromosomal gains and losses, while those carrying paracentric inversions usually produce unviable gametes [Madan, 1995]. In this current study, we present a newborn with dysmorphic features and malformations, whose karyotype showed an abnormal copy of chromomosome 7 described at first as add(7)(q32) as well as mos 45,X/47,XXX. Array comparative genomic hybridization (CGH) revealed an interstitial deletion in the long arm of chromosome 7 involving bands q35 to q36.3 but retaining the 7q subtelomere. The patient's deletion is believed to be due to meiotic recombination in the inversion loop in the phenotypically normal father who seems to carry two paracentric inversions in the long arm of chromosome 7,... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436155 Mon, 21 Nov 2011 05:00:00 +0100 5436155 http://www.medworm.com/index.php?rid=5436154&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34376 AbstractSchwannomatosis is a recently delineated inherited condition that has clinical overlap with neurofibromatosis type 2 (NF2). Diagnostic criteria have been developed to distinguish schwannomatosis from NF2, but the existence of mosaic NF2, which may closely mimic schwannomatosis, makes even these criteria problematic. In particular, it is not clear why there is a relative sparing of the cranial nerves from schwannomas in schwannomatosis. We have identified two individuals with schwannomatosis and a unilateral vestibular schwannoma (VS), where a diagnosis of NF2 has been excluded. A third case with an identified SMARCB1 mutation was reported by two radiologists to have a VS, but this was later confirmed as a jugular schwannoma. These cases question whether the current exclusion of a V... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436154 Mon, 21 Nov 2011 05:00:00 +0100 5436154 http://www.medworm.com/index.php?rid=5436153&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34371 In this study, the medical records of 75 Korean patients with Hunter syndrome (74 males, 1 female) were retrospectively reviewed to investigate the frequency of organ involvement and survival at a single center. The three most common symptoms of organ involvement were hepatosplenomegaly (99%), facial dysmorphism (97%), and frequent otitis media (91%). Cardiovascular involvement was also common including valvular abnormalities (89%), left ventricular hypertrophy (68%), and hypertension (30%). The 19 patients who died had a median age of 16.8 years at the time of death. Four of them died within 1 year of the start of enzyme replacement therapy; autopsy showed myocardial infarction with severe coronary artery disease in one patient. Two other patients died due to pneumonia and sleep apnea. In... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436153 Mon, 21 Nov 2011 05:00:00 +0100 5436153 http://www.medworm.com/index.php?rid=5436152&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34378 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436152 Mon, 21 Nov 2011 05:00:00 +0100 5436152 http://www.medworm.com/index.php?rid=5436151&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34373 AbstractBRESEK/BRESHECK syndrome is a multiple congenital malformation characterized by brain anomalies, intellectual disability, ectodermal dysplasia, skeletal deformities, ear or eye anomalies, and renal anomalies or small kidneys, with or without Hirschsprung disease and cleft palate or cryptorchidism. This syndrome has only been reported in three male patients. Here, we report on the fourth male patient presenting with brain anomaly, intellectual disability, growth retardation, ectodermal dysplasia, vertebral (skeletal) anomaly, Hirschsprung disease, low‐set and large ears, cryptorchidism, and small kidneys. These manifestations fulfill the clinical diagnostic criteria of BRESHECK syndrome. Since all patients with BRESEK/BRESHECK syndrome are male, and X‐linked syndrome of ichthyos... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436151 Mon, 21 Nov 2011 05:00:00 +0100 5436151 http://www.medworm.com/index.php?rid=5436150&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34375 This report shows that duplication of ZIC2 is not necessarily associated with brain malformations. We also describe the phenotype from four additional patients with duplications of the region of chromosome 13 containing ZIC2 and three previously described patients with supernumerary marker chromosomes derived from distal chromosome 13. None of the eight patients had holoprosencephaly or brain malformations, indicating that duplication of ZIC2 is not associated with brain anomalies. This information will be useful for counseling in other occurrences of this duplication identified by microarray. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436150 Mon, 21 Nov 2011 05:00:00 +0100 5436150 http://www.medworm.com/index.php?rid=5436149&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34369 The objective of this study was to systematically characterize the renal involvement in ALGS. We performed a retrospective review of 466 JAGGED1 mutation‐positive ALGS patients. Charts were reviewed for serum biochemistries, renal ultrasounds or other imaging, urinalysis, and clinical reports from pediatric nephrologists. The clinical data were reviewed by two pediatric hepatologists and a pediatric nephrologist. Of 466 charts reviewed we found 187 yielded evaluable renal information. Of these, 73/187 were shown to have renal involvement, representing 39% of the study cohort. Renal dysplasia was the most common anomaly seen. Genotype analysis of the JAGGED1 mutations in the patients with and without renal involvement did not reveal an association with mutation type. From the study we con... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5436149 Mon, 21 Nov 2011 05:00:00 +0100 5436149 http://www.medworm.com/index.php?rid=5394497&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34346 AbstractUnstable, gene‐rich pericentric regions have been associated with various structural aberrations including small supernumerary marker chromosomes (sSMCs). We hereby report on a complex pure mosaic sSMCs derived from chromosomes 11 and 19 in a child featuring multiple congenital anomalies. As indicated by microarray analysis, the sSMCs have involved materials from 11p11.12 → q12.1 and 19p12 → q12 in complex forms (with four cell lines harboring from 1 to 4 sSMCs) in all peripheral blood lymphocytes. The patient featured facial dysmorphism, generalized hypotonia, cryptorchidism, transverse palmar creases, cerebral hemorrhage, atrial septal defect secundum, strabismus, epilepsy, immunodeficiency, and severe cognitive and motor impairment. Literature review indicated this... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394497 Tue, 08 Nov 2011 05:00:00 +0100 5394497 http://www.medworm.com/index.php?rid=5394496&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34324 We report on a patient with a submicroscopic deletion of 12q13 detected by array‐CGH and confirmed by FISH. He was haploinsufficient for the HOXC gene cluster and some other neighboring genes. HOX genes have an important role in the initial formation of the body. The patient showed characteristic features including severe kyphoscoliosis, digital abnormalities, cardiac anomaly, expressive language, and global developmental delay. Radiologic features of the fingers had some similarities with those for multiple synostosis syndrome. No human genetic disorders due to HOXC abnormalities are yet known. We tentatively assume that his skeletal anomalies are associated with haploinsufficiency of the HOXC gene cluster. Further studies are necessary to determine the clinical importance of haploinsuf... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394496 Tue, 08 Nov 2011 05:00:00 +0100 5394496 http://www.medworm.com/index.php?rid=5394495&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34329 AbstractTo identify causes of death (COD) in propositi with Cornelia de Lange syndrome (CdLS) at various ages, and to develop guidelines to improve management and avoid morbidity and mortality, we retrospectively reviewed a total of 426 propositi with confirmed clinical diagnoses of CdLS in our database who died in a 41‐year period between 1966 and 2007. Of these, 295 had an identifiable COD reported to us. Clinical, laboratory, and complete autopsy data were completed on 41, of which 38 were obtainable, an additional 19 had autopsies that only documented the COD, and 45 propositi had surgical, imaging, or terminal event clinical documentation of their COD. Proband ages ranged from fetuses (21–40 weeks gestation) to 61 years. A literature review was undertaken to identify all reported ... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394495 Tue, 08 Nov 2011 05:00:00 +0100 5394495 http://www.medworm.com/index.php?rid=5394494&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34335 We report a 3‐month‐old boy ascertained for congenital scalp erosion and mild features of ectodermal dysplasia. His mother showed full‐blown characteristics of Rapp‐Hodgkin syndrome plus intense abdominal and popliteal freckling. Molecular investigation identified the novel TP63 mutation c.1697delG. We used a luciferase reporter assay to compare the effects on the p63 transactivation (TA) activity of c.1697delG with that of the p.Arg280Cys and p.Gln634X mutations, associated with ectrodactyly‐ectodermal dysplasia‐cleft lip/palate syndrome and isolated split hand/foot malformation, respectively. These results demonstrated complex behavior of c.1697delG in the TA of genes involved in epidermal differentiation and development and shed further light in the physiopathology of TP63�... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394494 Tue, 08 Nov 2011 05:00:00 +0100 5394494 http://www.medworm.com/index.php?rid=5394510&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34304 This study reports the findings from two large‐scale surveys among communities important to this biorepository. In the first, a population‐based phone survey of Nashville residents, we found that approval for BioVU is high (93.9%) and that this approval is similar among all population groups. A hypothetical biobank that does not obtain some form of written permission is much less well received. In the second, an online survey of Vanderbilt University faculty and staff, we found a higher level of support for BioVU (94.5%) among faculty and staff working throughout the university. In this survey, employees least likely to approve of BioVU are those employees who prefer not to receive medical care at Vanderbilt University. These surveys demonstrate the highest level of approval for a geno... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394510 Mon, 07 Nov 2011 05:00:00 +0100 5394510 http://www.medworm.com/index.php?rid=5394509&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34327 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394509 Mon, 07 Nov 2011 05:00:00 +0100 5394509 http://www.medworm.com/index.php?rid=5394508&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34310 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394508 Mon, 07 Nov 2011 05:00:00 +0100 5394508 http://www.medworm.com/index.php?rid=5394507&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34317 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394507 Mon, 07 Nov 2011 05:00:00 +0100 5394507 http://www.medworm.com/index.php?rid=5394506&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34328 AbstractEctrodactyly, ectodermal dysplasia, clefting (EEC) syndrome is the prototype of several p63 conditions, which include ankyloblepharon, ectodermal dysplasia, clefting (AEC) syndrome, limb‐mammary syndrome (LMS), Rapp‐Hodgkin syndrome (RHS), ADULT syndrome, and others. All these disorders include combinations of ectodermal dysplasia, orofacial clefting and limb malformations in variable severity. A newborn patient is presented with diffuse erythematous and desquamating skin lesions and anal atresia. She also had sparse and lightly colored thin hair, deeply set eyes, hypoplastic alae nasi, and a short philtrum. Cleft lip/palate and ankyloblepharon were not present. Complete cutaneous syndactyly was present on both hands in between the third and fourth fingers. Mild ectrodactyly wa... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394506 Mon, 07 Nov 2011 05:00:00 +0100 5394506 http://www.medworm.com/index.php?rid=5394505&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34330 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394505 Mon, 07 Nov 2011 05:00:00 +0100 5394505 http://www.medworm.com/index.php?rid=5394504&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34332 AbstractLife expectancy in vascular Ehlers–Danlos syndrome (EDS) is shortened due to spontaneous rupture of arteries, the colon and the gravid uterus. Two adolescent males with vascular EDS illustrate rapid progression of arterial aneurysms, dissections, and rupture. Radiologic imaging played an important role in initially diagnosing and monitoring the evolution of arterial involvement. Both prophylactic and emergency management remain largely ineffective in this connective tissue disorder; however, noninvasive imaging may provide important prognostic information. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394504 Mon, 07 Nov 2011 05:00:00 +0100 5394504 http://www.medworm.com/index.php?rid=5394503&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34333 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394503 Mon, 07 Nov 2011 05:00:00 +0100 5394503 http://www.medworm.com/index.php?rid=5394502&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34334 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394502 Mon, 07 Nov 2011 05:00:00 +0100 5394502 http://www.medworm.com/index.php?rid=5394501&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34336 This study illustrates the evolving genotype–phenotype relationship between the amount of progerin produced and the age of onset among the spectrum of restrictive dermopathy, HGPS, and atypical forms of WS. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394501 Mon, 07 Nov 2011 05:00:00 +0100 5394501 http://www.medworm.com/index.php?rid=5394500&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34345 AbstractFragile X E (FRAXE) is an X‐linked form of intellectual disability characterized by mild to moderate cognitive impairment, speech delay, hyperactivity, and autistic behavior. The folate‐sensitive fragile site FRAXE is located in Xq28 approximately 600 kb distal to the fragile X syndrome fragile site (FRAXA) and harbors an unstable GCC (CCG) triplet repeat adjacent to a CpG island in the 5′ untranslated region of the AFF2 (FMR2) gene. The disorder results from amplification and methylation of the GCC repeat and resultant silencing of AFF2. Although chromosome abnormalities that disrupt AFF2 have been reported in two individuals with mild‐moderate intellectual disability, microdeletions of Xq28 that delete only AFF2 have not been described as a potential cause of FRAXE‐in... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394500 Mon, 07 Nov 2011 05:00:00 +0100 5394500 http://www.medworm.com/index.php?rid=5394499&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34356 We report on a mother and son who were affected with split hand‐split foot (formerly described as ectrodactyly), ectodermal dysplasia, hyperpigmentation of skin, and dystrophic nails. Their hair was wiry, brownish, and slow‐growing. Scanning electron micrography of their scalp hair showed hypoplastic hair bulbs, partial loss of hair cuticles, and frayed hair shafts. The son was affected with amelogenesis Imperfecta (hypocalcification, hypoplasia, and hypomaturation types), in the primary and permanent dentition. An unerupted supernumerary maxillary second premolar and fusion of mandibular incisors were observed in the primary dentition and their permanent successors. Mutation analysis showed a c.588‐2A > C mutation in TP63 in the mother and her son. It is predicted that an alt... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394499 Mon, 07 Nov 2011 05:00:00 +0100 5394499 http://www.medworm.com/index.php?rid=5394498&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34303 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5394498 Mon, 07 Nov 2011 05:00:00 +0100 5394498 http://www.medworm.com/index.php?rid=5372201&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34318 AbstractThe panniculitides are a group of heterogeneous inflammatory diseases involving the subcutaneous fat, the pathogenesis of which is poorly understood. Here, we report on a female infant with Prader–Willi syndrome who developed a systemic inflammatory disorder in the neonatal period demonstrating recurrent panniculitis as a prominent feature. This is the second report of an association between Prader–Willi syndrome and panniculitis. Such an association might be explained by the unmasking of a recessive allele as a consequence of hemizygosity, in the case of a 15q11 deletion, or homozygosity, in the case of maternal isodisomy. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372201 Thu, 03 Nov 2011 04:00:00 +0100 5372201 http://www.medworm.com/index.php?rid=5372200&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34331 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372200 Thu, 03 Nov 2011 04:00:00 +0100 5372200 http://www.medworm.com/index.php?rid=5372199&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34290 AbstractWe evaluated a patient with mild intellectual disability, obesity, overgrowth, and dysmorphic features. Array comparative genomic hybridization (aCGH) analysis showed a single copy number increase of a BAC clone in the 11p15.4 region. Oligonucleotide aCGH refined the duplication to approximately 2.29 megabases (Mb) in size. Testing the parents revealed that the father, who had learning disabilities and overgrowth, also had the 11p15.4 duplication, and the mother had a normal microarray. In addition, the patient's brother and grandmother all share clinical features with the proband and tested positive for the duplication. The duplicated region (Chr11:6,934,067‐9,220,605) encompasses 29 genes, including the ZNF214 gene, which has been postulated to play a role in Beckwith–Wiede... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372199 Thu, 03 Nov 2011 04:00:00 +0100 5372199 http://www.medworm.com/index.php?rid=5372198&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34295 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372198 Thu, 03 Nov 2011 04:00:00 +0100 5372198 http://www.medworm.com/index.php?rid=5372197&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34296 We report on a male newborn with multiple congenital abnormalities consistent with the diagnosis of VACTERL association (vertebral, anal, cardiac, tracheo‐esophageal fistula, renal, and limb anomalies), who had Fanconi anemia (complementation group B) recognized by the detection of a deletion in chromosome Xp22.2 using an oligonucleotide array. The diagnosis of Fanconi anemia was confirmed by increased chromosomal breakage abnormalities observed in cultured cells that were treated with cross‐linking agents. This is the first report in the literature of Fanconi anemia complementation group B detected by oligonucleotide array testing postnatally. © 2011 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372197 Thu, 03 Nov 2011 04:00:00 +0100 5372197 http://www.medworm.com/index.php?rid=5372196&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34300 We report of a patient with partial trisomy 11q and partial monosomy 10p [46,XX,der(10)t(10;11)(p15;q22)] due to a paternal balanced translocation [46,XY,t(10;11)(p15;q22)]. Array CGH showed heterozygosity for a deletion of ∼3.46 Mb at 10p15.3p15.2 and gain of ∼32.21 Mb at 11q22.2q25. The patient, a 19‐year‐old woman, has a multiple congenital anomaly syndrome with severe developmental and growth delay, muscular hypotonia, iris coloboma, abnormal external ears, widely spaced nipples, atrial septum defect, clubfoot, and arthrogryposis multiplex congenita. Despite multiple health problems and numerous hospitalizations due to massive seizures, pulmonary insufficiency and recurrent infections the patient reached adulthood. The clinical features in our patient are compared to other ... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372196 Thu, 03 Nov 2011 04:00:00 +0100 5372196 http://www.medworm.com/index.php?rid=5372195&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34301 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372195 Thu, 03 Nov 2011 04:00:00 +0100 5372195 http://www.medworm.com/index.php?rid=5372194&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34302 In this report, we describe two new 17q23.2 deletion patients with mild intellectual disability and sensorineural hearing loss. They both had submicroscopic deletions smaller than the common deleted region for the 8 previously described 17q23.2 microdeletion cases. TBX4 was previously suggested as the responsible gene for the heart or limb defects observed in 17q23.2 deletion patients, but the present cases do not have these features despite deletion of this gene. The finding of sensorineural hearing loss in 5 of the 10 cases, including the present cases, with a microdeletion at17q23.2, strongly suggests the presence of a candidate gene for hearing loss within this region. We screened 41 patients with profound sensorineural hearing loss for mutations of TBX2 and detected no mutations. © 2... American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372194 Thu, 03 Nov 2011 04:00:00 +0100 5372194 http://www.medworm.com/index.php?rid=5372193&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34305 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372193 Thu, 03 Nov 2011 04:00:00 +0100 5372193 http://www.medworm.com/index.php?rid=5372192&cid=s_33747_50_f&fid=33747&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fajmg.a.34306 (Source: American Journal of Medical Genetics Part A) American Journal of Medical Genetics Part A journals http://www.medworm.com/rss/comments.php?id=5372192 Thu, 03 Nov 2011 04:00:00 +0100 5372192