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 'Journal of Medical Genetics' source. Thu, 09 Feb 2012 09:43:43 +0100 http://www.medworm.com/index.php?rid=5590822&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F146%3Frss%3D1 Conclusions Complete loss of expression of the ANT1 gene causes a clinical syndrome mainly characterised by cardiomyopathy and myopathy. This report expands the clinical spectrum of ANT1-related human diseases, and emphasises the crucial role of the mitochondrial ADP/ATP carriers in muscle function and pathophysiology of human myopathies. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590822 Thu, 12 Jan 2012 05:00:00 +0100 5590822 http://www.medworm.com/index.php?rid=5590821&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F138%3Frss%3D1 Conclusions This work confirms the importance of NOTCH2 as a second disease gene in ALGS and expands the repertoire of the NOTCH2 related disease phenotype. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590821 Thu, 12 Jan 2012 05:00:00 +0100 5590821 http://www.medworm.com/index.php?rid=5590820&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F126%3Frss%3D1 Conclusions CC2D2A testing should be prioritised in patients with JS and ventriculomegaly and/or seizures. Patients with CC2D2A-related JS should be monitored for hydrocephalus and seizures. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590820 Thu, 12 Jan 2012 05:00:00 +0100 5590820 http://www.medworm.com/index.php?rid=5590819&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F119%3Frss%3D1 Conclusions Genomic duplications encompassing BHLHA9 are associated with SHFLD and non-Mendelian inheritance characterised by a high degree of non-penetrance with sex bias. Knock-down of bhlha9 in zebrafish causes severe reduction defects of the pectoral fin, indicating a role for this gene in limb development. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590819 Thu, 12 Jan 2012 05:00:00 +0100 5590819 http://www.medworm.com/index.php?rid=5590818&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F110%3Frss%3D1 Conclusion The molecular characterisation of these patients suggests that the core cognitive features of the 15q24 microdeletion syndrome, including developmental delays and severe speech problems, are largely due to deletion of genes in a 1.1–Mb critical region. However, genes just distal to the critical region also play an important role in cognition and in the development of characteristic facial features associated with 15q24 deletions. Clearly, deletions in the 15q24 region are variable in size and extent. Knowledge of the breakpoints and size of deletion combined with the natural history and medical problems of our patients provide insights that will inform management guidelines. Based on common phenotypic features, all patients with 15q24 microdeletions should receive a thorou... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590818 Thu, 12 Jan 2012 05:00:00 +0100 5590818 http://www.medworm.com/index.php?rid=5590817&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F104%3Frss%3D1 Conclusion A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590817 Thu, 12 Jan 2012 05:00:00 +0100 5590817 http://www.medworm.com/index.php?rid=5590816&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F96%3Frss%3D1 Conclusion gamGWAS can effectively relieve the long gene bias and generate reliable results for GWAS data analysis. It does not require genotype data or permutation of sample labels in the original GWAS data; thus, it is computationally efficient. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590816 Thu, 12 Jan 2012 05:00:00 +0100 5590816 http://www.medworm.com/index.php?rid=5590815&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F90%3Frss%3D1 Conclusions At least two of the PCOS susceptibility loci identified in the Chinese PCOS GWAS (DENND1A and THADA) are also associated with PCOS in European derived populations, and are therefore likely to be important in the aetiology of PCOS regardless of ethnicity. The analysis of the LHCGR gene was not sufficiently powered to detect modest effects. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590815 Thu, 12 Jan 2012 05:00:00 +0100 5590815 http://www.medworm.com/index.php?rid=5590814&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F83%3Frss%3D1 Conclusion Mutant NDUFB9 is a new cause of complex I deficiency. A molecular diagnosis related to complex I deficiency was established in 18% of patients. However, most patients are likely to carry mutations in genes so far not associated with complex I function. The authors conclude that the high degree of genetic heterogeneity in complex I disorders warrants the implementation of unbiased genome-wide strategies for the complete molecular dissection of mitochondrial complex I deficiency. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590814 Thu, 12 Jan 2012 05:00:00 +0100 5590814 http://www.medworm.com/index.php?rid=5590813&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F79%3Frss%3D1 Conclusion This study shows that PKD, ICCA and some other PD-related phenotypes are part of the same phenotypic spectrum, caused by mutations in PRRT2. This underscores the complexity of the phenotypic consequences of PRRT2 mutations. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590813 Thu, 12 Jan 2012 05:00:00 +0100 5590813 http://www.medworm.com/index.php?rid=5590812&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F76%3Frss%3D1 Conclusion The present study identifies PRRT2 as the gene mutated in a subset of PKC, and suggests that PKC is genetically heterogeneous. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590812 Thu, 12 Jan 2012 05:00:00 +0100 5590812 http://www.medworm.com/index.php?rid=5590811&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F2%2F75%3Frss%3D1 If you are wondering why a Polychronakos would have any personal interest in the existence and universal adoption of a code that uniquely and unambiguously identifies authors of scientific papers, just do a PubMed search on my surname without my initial. There are four of us currently publishing: in addition to my C there is my brother V (an elementary-particle physicist), cousin A (ophthalmology) and another A, a prolific physicist whom I have never met. This does not include my late cousin D whose publications in obscure German or Greek journals can still be found at the chronological fringes of the PubMed search, or my father (yet another A) whose papers in French and Greek radiology journals date from the 1940s and never made it to PubMed. I can definitely sympathise with the Smith Js ... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5590811 Thu, 12 Jan 2012 05:00:00 +0100 5590811 http://www.medworm.com/index.php?rid=5499886&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F66%3Frss%3D1 Conclusions The authors' results extend to humans the seminal observations in RSTS mouse models and point to histone acetylation defects, mainly involving H2B and H2A, as relevant molecular markers of the disease. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499886 Tue, 13 Dec 2011 05:00:00 +0100 5499886 http://www.medworm.com/index.php?rid=5499885&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F58%3Frss%3D1 Conclusions The association of single-nucleotide polymorphisms in the TGFBR3 and BMP7 genes, which belong to the transforming growth factor β signalling pathway, suggests a role for this pathway in the pathogenesis of TDS. Integrating data from multiple layers can highlight findings in GWAS that are biologically relevant despite having border significance at currently accepted statistical levels. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499885 Tue, 13 Dec 2011 05:00:00 +0100 5499885 http://www.medworm.com/index.php?rid=5499884&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F47%3Frss%3D1 Conclusion The authors provide further insight into the phenotype of AOS with SMAD3 mutations, and present recommendations for a clinical work-up. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499884 Tue, 13 Dec 2011 05:00:00 +0100 5499884 http://www.medworm.com/index.php?rid=5499883&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F41%3Frss%3D1 Conclusions In patients presenting with an FSHD-like clinical phenotype with a negative molecular testing for FSHD, consider (1) detailed genetic testing including D4Z4 contraction of permissive hybrid D4Z4 repeat arrays, p13E-11 probe deletions, and D4Z4 hypomethylation in the absence of repeat contraction as observed in FSHD2; (2) mutations in CAPN3 even in the absence of protein deficiency on western blot analysis; and (3) VCP mutations even in the absence of cognitive impairment, Paget disease and typical inclusion in muscle biopsy. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499883 Tue, 13 Dec 2011 05:00:00 +0100 5499883 http://www.medworm.com/index.php?rid=5499882&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F37%3Frss%3D1 This study reports for the first time a patient with neonatal onset of PKD homozygous for an incomplete penetrant PKD2 missense variant due to uniparental disomy. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499882 Tue, 13 Dec 2011 05:00:00 +0100 5499882 http://www.medworm.com/index.php?rid=5499881&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F27%3Frss%3D1 Conclusions One or two pathogenic/likely pathogenic variants were identified in 86% of cases. No convincing cases of digenic inheritance were found. It is concluded that digenic inheritance does not make a significant contribution to Usher syndrome; the observation of multiple variants in different genes is likely to reflect polymorphic variation, rather than digenic effects. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499881 Tue, 13 Dec 2011 05:00:00 +0100 5499881 http://www.medworm.com/index.php?rid=5499880&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F21%3Frss%3D1 Discussion The mutation spectrum was similar in EVMPS and LMPS/FADS kindreds and EVMPS and LMPS phenotypes were observed in different families with the same CHRNG mutation. Despite this intrafamilial variability, it is estimated that there is a 95% chance that a subsequent sibling will have the same MPS phenotype (EVMPS or LMPS) as the proband (though concordance is less for more distant relatives). Based on these findings, a molecular genetic diagnostic pathway for the investigation of MPS/FADS is proposed. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499880 Tue, 13 Dec 2011 05:00:00 +0100 5499880 http://www.medworm.com/index.php?rid=5499879&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F16%3Frss%3D1 Conclusion This study identified the first intragenic DLX5 mutation in SHFM and raises interesting possibilities about a dual role for DLX5 in limb development. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499879 Tue, 13 Dec 2011 05:00:00 +0100 5499879 http://www.medworm.com/index.php?rid=5499878&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F10%3Frss%3D1 Conclusions The data show that homozygosity mapping and candidate gene analysis remain an efficient way to detect mutations even in small consanguineous pedigrees with OXPHOS deficiency, especially when the enzyme deficiency in fibroblasts allows appropriate candidate gene selection and functional complementation. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499878 Tue, 13 Dec 2011 05:00:00 +0100 5499878 http://www.medworm.com/index.php?rid=5499877&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F49%2F1%2F1%3Frss%3D1 An estimated 15–50% of the population experiences pain at any given time, at great personal and societal cost. Pain is the most common reason patients seek medical attention, and there is a high degree of individual variability in reporting the incidence and severity of symptoms. Research suggests that pain sensitivity and risk for chronic pain are complex heritable traits of polygenic origin. Animal studies and candidate gene testing in humans have provided some progress in understanding the heritability of pain, but the application of the genome-wide association methodology offers a new tool for further elucidating the genetic contributions to normal pain responding and pain in clinical populations. Although the determination of the genetics of pain is still in its infancy, it is c... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5499877 Tue, 13 Dec 2011 05:00:00 +0100 5499877 http://www.medworm.com/index.php?rid=5436126&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F864%3Frss%3D1 This is the second edition of this book, published first in 2007. It is the product of the joint efforts of a molecular geneticist, Professor Andrew Read, and a clinical geneticist, Professor Dian Donnai, both from the University of Manchester. As mentioned in the preface of the first edition, the ‘primary audience for this book is medical students’, but it is hoped that ‘it will also be useful for counsellors and scientists, and indeed established clinicians, who want an introduction to the place of clinical genetics in medicine and biology’. The present edition has kept the general spirit and structure of the first one. It is based on the presentation of clinical situations that illustrate important genetic disorders. As stated by the authors, the book has been de... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436126 Mon, 21 Nov 2011 05:00:00 +0100 5436126 http://www.medworm.com/index.php?rid=5436125&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F860%3Frss%3D1 Conclusions Intensive breast surveillance is therefore justified in these homozygous women. It is concluded that diagnostic testing for biallelic mutations in CHEK2 is indicated in non-BRCA1/2 breast cancer families, especially in populations with a relatively high prevalence of deleterious mutations in CHEK2. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436125 Mon, 21 Nov 2011 05:00:00 +0100 5436125 http://www.medworm.com/index.php?rid=5436124&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F856%3Frss%3D1 Conclusion This study reports a novel hereditary cancer syndrome caused by a germline BAP1 mutation that predisposes patients to UM, lung carcinoma, meningioma, and possibly other cancers. The results indicate that BAP1 is the candidate gene in only a small subset of hereditary UM, suggesting the contribution of other candidate genes. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436124 Mon, 21 Nov 2011 05:00:00 +0100 5436124 http://www.medworm.com/index.php?rid=5436123&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F851%3Frss%3D1 Conclusions Since the clinical significance of CI identified by aCGH might be influenced by such discrepancies between the two methods, these may in turn have an impact on clinical diagnosis and patient counselling. It is proposed that each genetic laboratory should evaluate the relevance of karyotyping for all first-tier abnormal aCGH results in order to include the genomic (chromosomal) aspects of the aCGH findings in the diagnosis. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436123 Mon, 21 Nov 2011 05:00:00 +0100 5436123 http://www.medworm.com/index.php?rid=5436122&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F840%3Frss%3D1 Conclusions The phenotypic similarities among subjects with int22h-1/int22h-2-mediated Xq28 duplications suggest that such duplications are responsible for a novel XLID syndrome. The reciprocal deletion may not be associated with a clinical phenotype in carrier females due to skewed XCI, but may be lethal for males in utero. Advancements in array CGH technology have enabled the identification of such small, clinically relevant copy-number variants. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436122 Mon, 21 Nov 2011 05:00:00 +0100 5436122 http://www.medworm.com/index.php?rid=5436121&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F831%3Frss%3D1 Conclusions These results demonstrate the utility of SNP genotyping data for detection of clinically significant abnormalities, including chimerism/mosaicism and recessive Mendelian disorders associated with autozygosity. The incidence of clinically significant low level mosaicism inferred from these cases suggests that this has hitherto been underestimated and chromosome mosaicism frequently occurs in the absence of indicative clinical features. The growing appreciation among clinicians and demand for SNP genotyping data poses significant challenges for the interpretation of LCSH, especially where there is no detailed phenotypic description to direct laboratory analysis. Finally, reporting of unexpected or hidden consanguinity revealed by SNP array analysis raises potential ethical and le... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436121 Mon, 21 Nov 2011 05:00:00 +0100 5436121 http://www.medworm.com/index.php?rid=5436120&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F825%3Frss%3D1 Conclusions These data indicate that a non-coding regulatory region critical for gonadal SOX9 expression and subsequent normal sex development is located far upstream of the SOX9 promoter. Its copy number variations are the genetic basis of isolated 46,XX and 46,XY DSDs of variable severity (ranging from mild to complete sex reversal). It is proposed that this region contains a gonad specific SOX9 transcriptional enhancer(s), the gain or loss of which results in genomic imbalance sufficient to activate or inactivate SOX9 gonadal expression in a tissue specific manner, switch sex determination, and result in isolated DSD. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436120 Mon, 21 Nov 2011 05:00:00 +0100 5436120 http://www.medworm.com/index.php?rid=5436119&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F819%3Frss%3D1 Conclusions There is a strong negative selective pressure against 22q11.2 deletions. This appears to be primarily mediated by the severity of the neuropsychiatric phenotype and an independent sexual selection effect. The latter also contributes to the observed excess of transmitting mothers. These results may have implications both for the evolutionary biology of this structural rearrangement and for genetic counselling and reproductive services for adolescents and adults with 22q11.2DS. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436119 Mon, 21 Nov 2011 05:00:00 +0100 5436119 http://www.medworm.com/index.php?rid=5436118&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F810%3Frss%3D1 Conclusions This study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA. A local effect at the synapse might be responsible. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436118 Mon, 21 Nov 2011 05:00:00 +0100 5436118 http://www.medworm.com/index.php?rid=5436117&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F802%3Frss%3D1 Conclusion This study identified new linkage regions at 20p13 (SIRPA and RNF24/PANK2 loci) and 2q33-q34 (IGFBP2 locus) for parameters describing morphology of the optic disc. The results of the study also suggested common genetic control of these parameters and RNFL thickness by SIX1 and doublecotin family genes. Finally, association signals for the recently reported RERE and LRP1B loci and the well known CDC7, TGFBR3, and ATOH7 loci were replicated. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436117 Mon, 21 Nov 2011 05:00:00 +0100 5436117 http://www.medworm.com/index.php?rid=5436116&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F12%2F793%3Frss%3D1 Fetal akinesia refers to a broad spectrum of disorders in which the unifying feature is a reduction or lack of fetal movement. Fetal akinesias may be caused by defects at any point along the motor system pathway including the central and peripheral nervous system, the neuromuscular junction and the muscle, as well as by restrictive dermopathy or external restriction of the fetus in utero. The fetal akinesias are clinically and genetically heterogeneous, with causative mutations identified to date in a large number of genes encoding disparate parts of the motor system. However, for most patients, the molecular cause remains unidentified. One reason for this is because the tools are only now becoming available to efficiently and affordably identify mutations in a large panel of disease genes... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5436116 Mon, 21 Nov 2011 05:00:00 +0100 5436116 http://www.medworm.com/index.php?rid=5342080&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F787%3Frss%3D1 Conclusion BTN2A1 may be a susceptible gene for MetS in Japanese individuals. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342080 Thu, 20 Oct 2011 04:00:00 +0100 5342080 http://www.medworm.com/index.php?rid=5342079&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F783%3Frss%3D1 Women who carry a pathogenic mutation in BRCA1 or BRCA2 have high risks of developing breast and ovarian cancers. The functional effect of many missense variants on BRCA1 and BRCA2 protein function is not known. Here, the authors construct a historical cohort of 4030 female first-degree relatives of 1345 unselected patients with ovarian cancer who have been screened for BRCA1 and BRCA2 mutations. The authors compared the risks by the age of 80 years for all cancers combined in female first-degree relatives of women with a pathogenic mutation, women with a variant of unknown significance (unclassified variant) and non-carriers. The cumulative risk of cancer among the relatives of patients with a pathogenic mutation was much higher than the risk in relatives of non-carriers (50.2% vs 28.5%; ... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342079 Thu, 20 Oct 2011 04:00:00 +0100 5342079 http://www.medworm.com/index.php?rid=5342078&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F779%3Frss%3D1 Conclusions This is the first reported case of a patient with CS carrying constitutional deletions in both the nuclear and the mitochondrial genome that might help elucidate some aspects of CS pathogenesis. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342078 Thu, 20 Oct 2011 04:00:00 +0100 5342078 http://www.medworm.com/index.php?rid=5342077&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F776%3Frss%3D1 Conclusion This indicates that rare de novo CNVs are increasingly being generated with advanced paternal age by replication based mechanisms during spermatogenesis. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342077 Thu, 20 Oct 2011 04:00:00 +0100 5342077 http://www.medworm.com/index.php?rid=5342076&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F767%3Frss%3D1 Conclusions One DFNB12 allele in trans configuration to an USH1D allele of CDH23 preserves vision and balance in deaf individuals, indicating that the DFNB12 allele is phenotypically dominant to an USH1D allele. This finding has implications for genetic counselling and the development of therapies for retinitis pigmentosa in Usher syndrome. Accession numbers The cDNA and protein Genbank accession numbers for CDH23 and cadherin 23 used in this paper are AY010111.2 and AAG27034.2, respectively. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342076 Thu, 20 Oct 2011 04:00:00 +0100 5342076 http://www.medworm.com/index.php?rid=5342075&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F761%3Frss%3D1 Conclusions This genotype–phenotype analysis explains some of the phenotypic variability in the syndrome and identifies new genomic regions with a high likelihood for causing important developmental phenotypes such as speech delay. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342075 Thu, 20 Oct 2011 04:00:00 +0100 5342075 http://www.medworm.com/index.php?rid=5342074&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F752%3Frss%3D1 Conclusions An algorithm is proposed based on these new phenotype–genotype correlations, to facilitate molecular analysis and genetic counselling for HPE. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342074 Thu, 20 Oct 2011 04:00:00 +0100 5342074 http://www.medworm.com/index.php?rid=5342073&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F741%3Frss%3D1 Conclusions These findings define the phenotypic spectrum associated with CASK loss-of-function mutations. The combination of developmental and brain imaging features together with mild facial dysmorphism is highly suggestive of this disorder and should prompt subsequent testing of the CASK gene. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342073 Thu, 20 Oct 2011 04:00:00 +0100 5342073 http://www.medworm.com/index.php?rid=5342072&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F737%3Frss%3D1 Conclusion NDUFA12 mutations are apparently not a frequent cause of complex I deficiency, since mutations were not found by screening altogether 122 complex I deficient patients in two different studies. NDUFA12 encodes an accessory subunit of complex I and is a paralogue of NDUFAF2. Despite the complete absence of NDUFA12 protein, a fully assembled and enzymatically active complex I could be found, albeit in reduced amounts. This suggests that NDUFA12 is required either at a late step in the assembly of complex I, or in the stability of complex I. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342072 Thu, 20 Oct 2011 04:00:00 +0100 5342072 http://www.medworm.com/index.php?rid=5342071&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F731%3Frss%3D1 Conclusions The current method has an advantage for the genetic diagnosis of Duchenne muscular dystrophy and Becker muscular dystrophy wherein a comprehensive mutational search may be feasible using a single platform. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342071 Thu, 20 Oct 2011 04:00:00 +0100 5342071 http://www.medworm.com/index.php?rid=5342070&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2F721%3Frss%3D1 The advances in next generation sequencing (NGS) technologies have had a significant impact on epigenomic research. The arrival of NGS technologies has enabled a more powerful sequencing based method—that is, ChIP-Seq—to interrogate whole genome histone modifications, improving on the conventional microarray based method (ChIP-chip). Similarly, the first human DNA methylome was mapped using NGS technologies. More importantly, studies of DNA methylation and histone modification using NGS technologies have yielded new discoveries and improved our knowledge of human biology and diseases. The concept that cytosine methylation was restricted to CpG dinucleotides has only been recently challenged by new data generated from sequencing the DNA methylome. Approximately 25% of all cytosi... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342070 Thu, 20 Oct 2011 04:00:00 +0100 5342070 http://www.medworm.com/index.php?rid=5342069&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F11%2Fe1%3Frss%3D1 We read with interest the article by Rivera-Brugués et al1 in a recent issue of this journal describing 3 patients out of 1523 patients with unexplained mental retardation. Analysis by whole genome array-CGH (comparative genomic hybridisation) showed an intragenic heterozygous deletion in the VPS13B gene, and the subsequent sequencing of the VPS13B gene revealed by one-point mutation in the second allele in all three patients. In a previous study, we screened the VPS13B gene in 34 patients (28 families) with a suspicion of Cohen syndrome and identified 14 different mutations in 8 families (12 patients).2 The mutations were found in a compound heterozygous state in five families and in a homozygous state in one consanguineous family. In two other families (patients P1-F1, P2-F2 and P... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5342069 Thu, 20 Oct 2011 04:00:00 +0100 5342069 http://www.medworm.com/index.php?rid=5244679&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F716%3Frss%3D1 Conclusions FFDD type III heterozygotes with TWIST2 mutations may have syndromic manifestations. Review of previous FFDD patients resulted in reclassification of the subtypes. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244679 Mon, 19 Sep 2011 04:00:00 +0100 5244679 http://www.medworm.com/index.php?rid=5244678&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F713%3Frss%3D1 Conclusions This case demonstrates that DARS2 mutation homozygosity is not lethal, as suggested earlier, but compatible with a rather benign disease course. More importantly, it extends the phenotypic spectrum of LBSL and reveals that at least some DARS2-associated phenotypic features might be readily treatable. However, future observations of paroxsymal ataxia and, possibly, areflexia in other DARS2-mutated patients are warranted to further corroborate our finding that DARS2 mutations can lead to a paroxsymal ataxia phenotype. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244678 Mon, 19 Sep 2011 04:00:00 +0100 5244678 http://www.medworm.com/index.php?rid=5244677&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F710%3Frss%3D1 Conclusions Our results confirm that even in absence of SRY, complete male differentiation may occur, possibly driven by overexpression of SOX9 in the gonadal ridge, as a consequence of the amplification of a gene desert region. We hypothesize that this region contains gonadal specific long-range regulation elements whose alteration may impair the normal sex development. Our data show that normal XX males, with alteration in copy number or, possibly, in the critical sequence upstream to SOX9 are a new category of infertility inherited in a dominant way with expression limited to the XX background. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244677 Mon, 19 Sep 2011 04:00:00 +0100 5244677 http://www.medworm.com/index.php?rid=5244676&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F705%3Frss%3D1 Conclusion These findings support the idea that genetic variants affecting the FGF10 signalling pathway are important determinants of lung function that may ultimately contribute to COPD. Specifically, the results show that FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244676 Mon, 19 Sep 2011 04:00:00 +0100 5244676 http://www.medworm.com/index.php?rid=5244675&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F703%3Frss%3D1 The rare variant rs12975333 is a G->T change located at the eighth nucleotide of the mature microRNA-125a (miR-125a). The T allele has been reported to block the processing of pri-miRNA to pre-miRNA precursor and to be extremely rare, being detected only once in a panel of 1200 individuals from diverse ethnic backgrounds assessed by the Centre d'Etude du Polymorphisme Humain.1 A study by Li et al2 showed the T allele of rs12975333 to be strongly associated with breast cancer risk, with 6 of 72 (8.3%) breast cancer cases from two hospitals in Antwerp, Belgium, being carriers of the T allele and none of 282 controls collected from the general population in the Antwerp area or 587 Caucasian controls collected in the USA.2 The breast cancers were all lymph node negative and received only lo... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244675 Mon, 19 Sep 2011 04:00:00 +0100 5244675 http://www.medworm.com/index.php?rid=5244674&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F698%3Frss%3D1 Conclusion This may be the first common susceptibility allele for breast cancer to be identified with a recessive mode of inheritance. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244674 Mon, 19 Sep 2011 04:00:00 +0100 5244674 http://www.medworm.com/index.php?rid=5244673&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F691%3Frss%3D1 Conclusions The authors report a case of fatal infantile HCM caused by missense mutations in NDUFAF1 associated with complex I misassembly. Establishing a genetic diagnosis in mitochondrial cardiomyopathy is challenging and achieved in only a minority of cases because of complex genetics. A precise genetic diagnosis is important to provide accurate prognostic and genetic counselling advice regarding recurrence risks and to guide future reproductive options. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244673 Mon, 19 Sep 2011 04:00:00 +0100 5244673 http://www.medworm.com/index.php?rid=5244672&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F682%3Frss%3D1 The authors report here the clinical, genetic, molecular and biochemical characterisation of a large five-generation Han Chinese pedigree with maternally transmitted non-syndromic hearing loss. 17 of 35 matrilineal relatives exhibited variable severity and age at onset of sensorineural hearing loss. The average age at onset of hearing loss in matrilineal relatives of this family is 29 years, while matrilineal relatives among families carrying other mitochondrial DNA mutations developed hearing loss with congenital conditions or early age at onset. Molecular analysis of their mitochondrial genome identified the novel heteroplasmic T12201C mutation in the transfer RNA (tRNA)His gene. The levels of T12201C mutation in matrilineal relatives of this family correlated with the severity and ... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244672 Mon, 19 Sep 2011 04:00:00 +0100 5244672 http://www.medworm.com/index.php?rid=5244671&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F669%3Frss%3D1 In conclusion, POLG mutations account for a broad clinical spectrum of mitochondrial disorders. Sequence analysis of the POLG gene should be considered as a part of routine screening for mitochondrial disorders, even in the absence of apparent mitochondrial DNA abnormalities. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244671 Mon, 19 Sep 2011 04:00:00 +0100 5244671 http://www.medworm.com/index.php?rid=5244670&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F660%3Frss%3D1 Conclusions Benign COX deficiency is better described as ‘reversible infantile respiratory chain deficiency’. It is genetically heterogeneous, and patients not carrying the m.14674T>C or T>G mt-tRNAGlu mutations may have mutations in the TRMU gene. Diagnosing this disorder at the molecular level is a significant advance for paediatric neurologists and intensive care paediatricians, enabling them to select children with an excellent prognosis for continuing respiratory support from those with severe mitochondrial presentation in infancy. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244670 Mon, 19 Sep 2011 04:00:00 +0100 5244670 http://www.medworm.com/index.php?rid=5244669&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F651%3Frss%3D1 Among the hereditary ataxias, autosomal recessive cerebellar ataxias (ARCAs) encompass a diverse group of rare neurodegenerative disorders in which a cerebellar syndrome is the key clinical feature. The clinical overlap between the different cerebellar ataxias, the occasional atypical phenotypes, and the genetic heterogeneity often complicate the clinical management of such patients. Despite the steady increase in newly discovered ARCA genes, many patients with a putative ARCA cannot be genotyped yet, proving that more genes must be involved. This review presents an updated overview of the various ARCAs. The clinical and genetic characteristics of those forms with a known molecular genetic defect are discussed, along with the emerging insights in the underlying pathophysiological mechanism... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244669 Mon, 19 Sep 2011 04:00:00 +0100 5244669 http://www.medworm.com/index.php?rid=5244668&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F10%2F649%3Frss%3D1 The availability of predictive genetic tests has rapidly expanded in the last two decades. We can now provide testing for a range of adult onset conditions including certain cancers, cardiac diseases, and neurological disorders. These developments have recognised benefit including determining the necessity of additional screening or preventive options, relieving uncertainty, and reproductive planning. However, despite these benefits, predictive tests raise challenges regarding the ethical delivery of genetic testing, results, and services. To respond to these challenges, predictive testing protocols, such as those for Huntington disease (HD), have required several in-person appointments, spread over several weeks or months, in order to undergo counselling, testing, and receive test results... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5244668 Mon, 19 Sep 2011 04:00:00 +0100 5244668 http://www.medworm.com/index.php?rid=5153343&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F645%3Frss%3D1 Conclusions Both FOXE1 and NKX2-1 were associated with the increased risk of sporadic Japanese PTC. No clear associations were observed for either SNP with BRAFV600E status. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153343 Mon, 22 Aug 2011 23:00:00 +0100 5153343 http://www.medworm.com/index.php?rid=5153342&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F640%3Frss%3D1 This report describes a patient with junctional epidermolysis bullosa who was expected to die because of compound heterozygous nonsense mutations in the gene LAMA3 (R943X/R1159X), but was rescued by spontaneous read-through of the R943X allele. Results and conclusion FACS analysis of cells carrying various PTCs surrounded by their natural neighbouring codons revealed significant reporter gene expression despite the PTC only for this patient's genetic context. Gene expression could be abolished by replacing the first or third nucleotide before, or one of the two nucleotides following the PTC. Site-directed mutagenesis was used to identify genotypes allowing PTC read-through. The genetic context of the LAMA3 mutation R943X is close to a hypothetical consensus sequence for maximum PTC read-t... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153342 Mon, 22 Aug 2011 23:00:00 +0100 5153342 http://www.medworm.com/index.php?rid=5153341&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F635%3Frss%3D1 Conclusion Isolated duplications of distal 11q region have been previously reported and associated with intellectual disability but without a consistent set of clinical features. These findings support the proposal that microtriplication 11q24.1 is a well recognisable clinical entity. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153341 Mon, 22 Aug 2011 23:00:00 +0100 5153341 http://www.medworm.com/index.php?rid=5153340&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F629%3Frss%3D1 Conclusions The results suggest a mutual control of serum hepcidin and ferritin concentrations, a mechanism relevant to the pathophysiology of HFE haemochromatosis, and demonstrate that the HFE rs1800562 C282Y variant exerts a direct pleiotropic effect on the iron parameters, in part independent of hepcidin. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153340 Mon, 22 Aug 2011 23:00:00 +0100 5153340 http://www.medworm.com/index.php?rid=5153339&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F618%3Frss%3D1 Conclusion From this the largest published comprehensive cohort of IBMFSs, it can be concluded that recent advances have led to successful genotyping of about half of the patients. Establishing a genetic diagnosis is still challenging and there is a critical need to develop novel diagnostic tools. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153339 Mon, 22 Aug 2011 23:00:00 +0100 5153339 http://www.medworm.com/index.php?rid=5153338&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F610%3Frss%3D1 Conclusion These data indicate that 4% of adult mitochondrial disease with multiple deletions is caused by RNR dysfunction. KSS has not previously been linked to a nuclear gene defect. Evidence that disease pathogenesis may be caused by defective RNR assembly is given. RRM2B screening should be considered early in the differential diagnosis of adults with multiple mtDNA deletions. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153338 Mon, 22 Aug 2011 23:00:00 +0100 5153338 http://www.medworm.com/index.php?rid=5153337&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F606%3Frss%3D1 Conclusion Single-lane exome next-generation sequencing is sufficient to fully analyse all the transcripts of the X chromosome. This method is particularly suitable for mutation screening of X-linked recessive disorders and can avoid biases in candidate gene choice. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153337 Mon, 22 Aug 2011 23:00:00 +0100 5153337 http://www.medworm.com/index.php?rid=5153336&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F602%3Frss%3D1 Conclusion These results suggest that ACSF3 is a candidate gene for non-classical CMAMMA observed in our patients and document the value of exome sequencing of a limited number of patients for the identification of novel disease genes. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153336 Mon, 22 Aug 2011 23:00:00 +0100 5153336 http://www.medworm.com/index.php?rid=5153335&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F597%3Frss%3D1 Conclusion The power of combining exome and autozygome analysis in the study of genetics of autosomal recessive disorders, even in simplex cases, has been demonstrated. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153335 Mon, 22 Aug 2011 23:00:00 +0100 5153335 http://www.medworm.com/index.php?rid=5153334&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F593%3Frss%3D1 Communication We identified a 28-year-old cognitively normal patient with severe visual loss, absent electrical signals from the photoreceptors by electroretinogram (ERG) and nystagmus due to Leber congenital amaurosis (LCA), associated with hearing loss and Arnold–Chiari malformation. Exome sequencing detected a homozygous PEX1 mutation (p.Gly843Asp). Within a large LCA cohort, we found the mutation again in a 9-month-old baby. Peroxisome biochemical studies on both patients confirmed a peroxisome biogenesis disorder (PBD) in the Zellweger spectrum. We thus demonstrate that these patients, who had isolated LCA on presentation, actually had PBD as the cause of their LCA. Furthermore, the phenotype of the first patient was outside that of a typical Zellweger spectrum, and exome sequen... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153334 Mon, 22 Aug 2011 23:00:00 +0100 5153334 http://www.medworm.com/index.php?rid=5153333&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F590%3Frss%3D1 Conclusion This patient represents the first case of an inborn error of folate metabolism affecting the trifunctional MTHFD1 protein. This report reinforces the power of exome capture and sequencing for the discovery of novel genes, even when only a single proband is available for study. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153333 Mon, 22 Aug 2011 23:00:00 +0100 5153333 http://www.medworm.com/index.php?rid=5153332&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F580%3Frss%3D1 Recent advances in next-generation sequencing technologies have brought a paradigm shift in how medical researchers investigate both rare and common human disorders. The ability cost-effectively to generate genome-wide sequencing data with deep coverage in a short time frame is replacing approaches that focus on specific regions for gene discovery and clinical testing. While whole genome sequencing remains prohibitively expensive for most applications, exome sequencing—a technique which focuses on only the protein-coding portion of the genome—places many advantages of the emerging technologies into researchers' hands. Recent successes using this technology have uncovered genetic defects with a limited number of probands regardless of shared genetic heritage, and are changing ou... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153332 Mon, 22 Aug 2011 23:00:00 +0100 5153332 http://www.medworm.com/index.php?rid=5153331&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F579%3Frss%3D1 The power of massively parallel sequencing (MPS) combined with target enrichment technologies has led, in the space of barely 2 years, to a true revolution in our ability to explore the genome for sequence changes responsible for phenotypes of interest. While the resequencing efforts in search of low-frequency variants involved in complex traits have only generated hopes to date, targeted sequencing can claim one resounding success: the rate at which reports are appearing that identify the gene mutated in rare monogenic diseases is astounding and growing by the month. The sequencing of coding exons and adjacent splicing elements, sites of the vast majority of mutations responsible for Mendelian diseases, is now a routine and relatively inexpensive procedure, blurring the distinction b... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153331 Mon, 22 Aug 2011 23:00:00 +0100 5153331 http://www.medworm.com/index.php?rid=5153330&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F9%2F577%3Frss%3D1 In a seminal article in 2007, Ropers presented new perspectives for the elucidation of genetic disorders.1 He states what clinical geneticists have known for years—that Mendelian disorders, and in particular, autosomal recessive disorders, deserve more attention. Online Mendelian Inheritance in Man (OMIM) indicates that there are 1638 autosomal phenotypes for which the molecular basis is unknown. Historically, such disorders have been neglected, both because of their rarity and because of the difficulty in identifying the underlying genes and mutations. Recently, exome capture and sequencing has been shown to be a feasible approach to identifying disease mutations,2–4 in theory using only a single patient. Thus a systematic programme to discover all of these genes is an appropr... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5153330 Mon, 22 Aug 2011 23:00:00 +0100 5153330 http://www.medworm.com/index.php?rid=5046524&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F576%3Frss%3D1 Gardie B, Remenieras A, Kattygnarath D, et al. Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma. J Med Genet 2011;48:226–34. In figure 3, the terms "Kidney cancer" and "Uterine leiomyomas" were inverted. The corrected version of this figure is published below. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046524 Wed, 20 Jul 2011 23:00:00 +0100 5046524 http://www.medworm.com/index.php?rid=5046523&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F572%3Frss%3D1 Conclusions Although next-generation sequencing will replace all large-scale sequencing platforms for inherited cardiac disorders in the near future, this HCM resequencing array is currently the most rapid, cost-effective and reasonably efficient technology for first-tier mutation screening of HCM in clinical practice. Because of its design, the array is also an appropriate tool for initial screening of other inherited forms of cardiomyopathy. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046523 Wed, 20 Jul 2011 23:00:00 +0100 5046523 http://www.medworm.com/index.php?rid=5046522&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F567%3Frss%3D1 Conclusions The S/EmpP approach is a flexible and powerful approach that can be applied to linkage analysis of families with suspected Mendelian disorders. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046522 Wed, 20 Jul 2011 23:00:00 +0100 5046522 http://www.medworm.com/index.php?rid=5046521&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F563%3Frss%3D1 Conclusion This is the first study to report that the 57 kb deletion extends into the TRPV1 gene causing dysregulation of transcription in PBMC isolated from cystinosis patients. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046521 Wed, 20 Jul 2011 23:00:00 +0100 5046521 http://www.medworm.com/index.php?rid=5046520&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F557%3Frss%3D1 Conclusions This study has identified QTLs and putative candidate genes of murine AIP. Their functional role and relevance to human AIP will be studied further. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046520 Wed, 20 Jul 2011 23:00:00 +0100 5046520 http://www.medworm.com/index.php?rid=5046519&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F549%3Frss%3D1 Conclusions PDE10A or DACT2 were identified as candidate genes contributing to hyperthyrotropinaemia (and possibly hypothyroidism) in this sample. Studies in additional populations support association of variants at this locus with TSH values, especially in the PDE10A gene. Genetic linkage in families with hyperthyrotropinaemia suggests the presence of functional variants that contribute to pathological disruption of the hypothalamus–pituitary–thyroid axis. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046519 Wed, 20 Jul 2011 23:00:00 +0100 5046519 http://www.medworm.com/index.php?rid=5046518&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F540%3Frss%3D1 Conclusions The authors recommend close follow-up of patients with NLRP7 mutations and rare NSVs to prevent the death of the rare or reduced number of babies that reach term. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046518 Wed, 20 Jul 2011 23:00:00 +0100 5046518 http://www.medworm.com/index.php?rid=5046517&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F535%3Frss%3D1 Conclusions This new technology raises the possibility of unexpected findings in cancer predisposition genes. Therefore, the possibility of such findings has to be addressed in pre-test and post-test counselling by genetically trained healthcare professionals. As many of these findings have not been described previously, their clinical significance is unknown and patients need long-term follow-up to determine their clinical relevance. This will enable genetic healthcare professionals to advise such people about their cancer risks and appropriate cancer risk management options. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046517 Wed, 20 Jul 2011 23:00:00 +0100 5046517 http://www.medworm.com/index.php?rid=5046516&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F530%3Frss%3D1 Conclusion De novo MMR gene mutations are uncommon causes of Lynch syndrome. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046516 Wed, 20 Jul 2011 23:00:00 +0100 5046516 http://www.medworm.com/index.php?rid=5046515&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F526%3Frss%3D1 Conclusion The findings demonstrate the value of the PTT in identifying mosaic mutations in apparently APC mutation negative FAP patients with de novo classical polyposis and the need to keep the PTT within the diagnostic repertoire for APC mutation analysis. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046515 Wed, 20 Jul 2011 23:00:00 +0100 5046515 http://www.medworm.com/index.php?rid=5046514&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F523%3Frss%3D1 Conclusion Mutations within the PALB2 gene are rare events that do not account for a substantial proportion of cancer susceptibility in breast–pancreas cancer families. Routine screening of breast–pancreas cancer families for the presence of PALB2 mutations appears to be low yield. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046514 Wed, 20 Jul 2011 23:00:00 +0100 5046514 http://www.medworm.com/index.php?rid=5046513&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F520%3Frss%3D1 Triple negative breast cancer (TNBC) is a term that reflects lack of immunostaining for oestrogen, progesterone, and HER2 receptors. It is a relatively uncommon subgroup of breast cancers, accounting for approximately 15% of all types, and overlaps substantially with basal tumours (defined by gene expression pattern) that are the predominant tumour that develops in BRCA1 mutation carriers.1 TNBCs usually have a worse prognosis and no clear options for receptor targeted treatment.2 The recent development of drugs that target the homologous recombination repair deficiency typical of BRCA-null cancer cells has led to an increased referral of women who have developed TNBC to genetic services for (rapid) genetic testing.3 We have tested 63 isolated cases of TNBC <41 years and only eight... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046513 Wed, 20 Jul 2011 23:00:00 +0100 5046513 http://www.medworm.com/index.php?rid=5046512&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F513%3Frss%3D1 Background A positive family history, germline mutations in DNA mismatch repair genes, tumours with high microsatellite instability, and loss of mismatch repair protein expression are the hallmarks of hereditary non-polyposis colorectal cancer (Lynch syndrome). However, in ~10–15% of cases of suspected Lynch syndrome, no disease-causing mechanism can be detected. Methods Oligo array analysis was performed to search for genomic imbalances in patients with suspected mutation-negative Lynch syndrome with MLH1 deficiency in their colorectal tumours. Results and conclusion A deletion in the LRRFIP2 (leucine-rich repeat flightless-interacting protein 2) gene flanking the MLH1 gene was detected, which turned out to be a paracentric inversion on chromosome 3p22.2 creating two new stable fu... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046512 Wed, 20 Jul 2011 23:00:00 +0100 5046512 http://www.medworm.com/index.php?rid=5046511&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F8%2F505%3Frss%3D1 Conclusion The mutation frequency in patients meeting CS diagnostic criteria (34%) was significantly lower than previously reported, suggesting a need for reevaluation of these criteria. A mutation prediction model has been developed which can help identify patients appropriate for PTEN testing in clinical practice. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5046511 Wed, 20 Jul 2011 23:00:00 +0100 5046511 http://www.medworm.com/index.php?rid=4958456&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F497%3Frss%3D1 Conclusion These results suggest that genomic alteration of RET or GDNF is not a major mechanism leading to renal agenesis and other severe kidney development defects. Analysis of a larger series of patients will be necessary to validate the association of the RET intron 1 variant rs2506012 with renal development defects. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958456 Tue, 21 Jun 2011 23:00:00 +0100 4958456 http://www.medworm.com/index.php?rid=4958455&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F493%3Frss%3D1 Conclusions Expression differences between treated CD patients and controls along with SNP expression associations suggest a possible primary role for these four genes and their variants in pathogenesis. The lack of SNP effect in the remaining genes is probably a consequence of arbitrary candidate gene selection within association signals that are not based on functional studies. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958455 Tue, 21 Jun 2011 23:00:00 +0100 4958455 http://www.medworm.com/index.php?rid=4958454&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F485%3Frss%3D1 Conclusions This study identified at least two independent protective effects which are tagged by A*02–Cw*05 and A*02, respectively. Further studies are needed to elucidate whether this protective effect is due to the presence of an unanalysed factor characterising the HLA extended haplotype(s) carrying A*02 and Cw*05 or to a direct interaction between these alleles. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958454 Tue, 21 Jun 2011 23:00:00 +0100 4958454 http://www.medworm.com/index.php?rid=4958453&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F477%3Frss%3D1 Conclusions These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958453 Tue, 21 Jun 2011 23:00:00 +0100 4958453 http://www.medworm.com/index.php?rid=4958452&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F473%3Frss%3D1 Conclusion This study provides evidence for replication of recent genome-wide association studies results and shows that variants in or near BAK1, DMRT1, TERT-CLPTM1L, and KITLG predispose to familial and bilateral TGCT. These findings imply that familial TGCT and sporadic TGCT share a common genetic basis. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958452 Tue, 21 Jun 2011 23:00:00 +0100 4958452 http://www.medworm.com/index.php?rid=4958451&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F467%3Frss%3D1 Conclusion These genetic data suggest that ABCC4 could play a fundamental role in KD pathogenesis with effects on immune activation and vascular response to injury. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958451 Tue, 21 Jun 2011 23:00:00 +0100 4958451 http://www.medworm.com/index.php?rid=4958450&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F462%3Frss%3D1 Conclusions This is the first demonstration of a genetic influence on RLS in ESRD patients with BTBD9 being significantly associated. The extent of the genetic predisposition could vary between different subgroups of RLS in ESRD. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958450 Tue, 21 Jun 2011 23:00:00 +0100 4958450 http://www.medworm.com/index.php?rid=4958449&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F458%3Frss%3D1 Conclusions These findings confirm that gastrointestinal polyps are a common manifestation of MAS, indicate an overlap between MAS and PJS, and point towards a putative interaction between the GNAS and STK11 genes in the pathogenesis of these two disorders. The findings suggest a need for routine gastrointestinal endoscopy in patients with MAS, to establish the true incidence of polyps in these patients. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958449 Tue, 21 Jun 2011 23:00:00 +0100 4958449 http://www.medworm.com/index.php?rid=4958448&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F450%3Frss%3D1 Conclusions In contrast to complete null phenotypes, presence of minor amounts of collagen XVII protein in JEB skin is associated with mild phenotypic manifestations. The data have significant implications for design of molecular therapies for JEB, since they suggest that already a low extent of collagen XVII restoration will improve skin stability and alleviate symptoms. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958448 Tue, 21 Jun 2011 23:00:00 +0100 4958448 http://www.medworm.com/index.php?rid=4958447&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F444%3Frss%3D1 Conclusions These results strengthen the association between paediatric chordoma and TSC. Future clinical and molecular studies documenting the magnitude and clinical spectrum of the joint occurrence of these two diseases should provide the basis for delineating the biological relationship between them. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958447 Tue, 21 Jun 2011 23:00:00 +0100 4958447 http://www.medworm.com/index.php?rid=4958446&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F438%3Frss%3D1 Conclusion This non-CTG configuration expands current understanding of the sequence variations that can arise at this hypermutable site. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958446 Tue, 21 Jun 2011 23:00:00 +0100 4958446 http://www.medworm.com/index.php?rid=4958445&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F7%2F433%3Frss%3D1 Discussion The received wisdom that non-disjunction is the primary mechanism leading to human aneuploidy should be reconsidered. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4958445 Tue, 21 Jun 2011 23:00:00 +0100 4958445 http://www.medworm.com/index.php?rid=4869506&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F426%3Frss%3D1 Conclusions In contrast to prior reports on non-genotyped hypohidrotic ectodermal dysplasia populations, this study confirmed a consistent, quantifiable defect of sweat gland function in male XLHED subjects as a disease biomarker. Among 26 different EDA genotypes, specific mutations were shown to be consistently associated with anhidrosis, implying that systematic mapping of EDA mutations together with the analysis of objective clinical data may help to distinguish functionally crucial mutations from those allowing residual activity of the gene product. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869506 Tue, 24 May 2011 23:00:00 +0100 4869506 http://www.medworm.com/index.php?rid=4869505&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F422%3Frss%3D1 Conclusion This study demonstrates the sensitivity and specificity of this technology to accurately identify 99% of LSD patients, with the exception of one MPS II false negative. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869505 Tue, 24 May 2011 23:00:00 +0100 4869505 http://www.medworm.com/index.php?rid=4869504&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F421%3Frss%3D1 Neves-Pereira M, Müller B, Massie D, Williams JHG, O'Brien PCM, Hughes A, Shen S-B, St Clair D, Miedzybrodzka Z. Deregulation of EIF4E: a novel mechanism for autism. J Med Genet 2009;46:759–65. Prof David St Clair and Dr Zosia Miedzybrodzka should have been co-corresponding authors on this paper. Their contact details are shown below: Prof David St Clair, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland, UK; d.stclair@abdn.ac.uk Dr Zosia Miedzybrodzka, University of Aberdeen, Department of Genetics, Polwarth Building Foresterhill, Aberdeen, Scotland, UK; zosia@abdn.ac.uk (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869504 Tue, 24 May 2011 23:00:00 +0100 4869504 http://www.medworm.com/index.php?rid=4869503&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F417%3Frss%3D1 Conclusions It is concluded that GD is a genetically heterogeneous condition. Ongoing studies will hopefully lead to the identification of another disease gene. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869503 Tue, 24 May 2011 23:00:00 +0100 4869503 http://www.medworm.com/index.php?rid=4869502&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F413%3Frss%3D1 Discussion FOXN1 is crucial for in utero T cell development in humans. The identification of a limited number of CD8+ cells suggests an extrathymic origin for these cells, implying FOXN1-independent lymphopoiesis. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869502 Tue, 24 May 2011 23:00:00 +0100 4869502 http://www.medworm.com/index.php?rid=4869501&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F407%3Frss%3D1 Conclusions SCA15 is the most common non-trinucleotide repeat SCA in Central Europe. Screening for ITPR1 deletions should be considered in patients with slowly progressive SCA, vermal cerebellar atrophy and prominent tremor after excluding common SCA repeat expansions. Promoter and exon 2 of ITPR1 may be preserved from the deletion in some cases of SCA15. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869501 Tue, 24 May 2011 23:00:00 +0100 4869501 http://www.medworm.com/index.php?rid=4869500&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F396%3Frss%3D1 Conclusions These findings have significantly expanded the number of FOXG1 mutations and identified two affecting possible cis-regulatory elements. While the phenotype of the patients overlaps both classic and congenital Rett syndrome, extensive clinical evaluation demonstrates a distinctive and clinically recognisable phenotype which the authors suggest designating as the FOXG1 syndrome. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869500 Tue, 24 May 2011 23:00:00 +0100 4869500 http://www.medworm.com/index.php?rid=4869499&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F390%3Frss%3D1 Conclusions The results indicate that Sensenbrenner syndrome is caused by disrupted IFT-A-mediated retrograde ciliary transport. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869499 Tue, 24 May 2011 23:00:00 +0100 4869499 http://www.medworm.com/index.php?rid=4869498&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F383%3Frss%3D1 Conclusions The abundant expression of PIGN in various tissues is compatible with the diverse phenotypic features observed in the patients and with the involvement of multiple body systems. The presence of developmental delay, hypotonia, and epilepsy combined with multiple congenital anomalies, especially anorectal anomalies, should lead a clinician to suspect a GPI deficiency related disorder. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869498 Tue, 24 May 2011 23:00:00 +0100 4869498 http://www.medworm.com/index.php?rid=4869497&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F375%3Frss%3D1 Conclusions The milder phenotypes associated with FREM1 deficiency in humans (MOTA syndrome and BNAR syndrome) compared to that resulting from FRAS1 and FREM2 loss of function (Fraser syndrome) are also consistent with the less severe phenotypes resulting from Frem1 loss of function in mice. Together, Fraser, BNAR and MOTA syndromes constitute a clinically overlapping group of FRAS–FREM complex diseases. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869497 Tue, 24 May 2011 23:00:00 +0100 4869497 http://www.medworm.com/index.php?rid=4869496&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F369%3Frss%3D1 Conclusion These results provide new insights into the molecular basis of hearing function and may suggest new targets for hearing impairment treatment and prevention. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869496 Tue, 24 May 2011 23:00:00 +0100 4869496 http://www.medworm.com/index.php?rid=4869495&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F6%2F361%3Frss%3D1 Panic disorder (PD) is one of the most common anxiety disorders, with a prevalence of 3.4–4.7%. Although PD seems to have no known cause, and its underlying aetiology is not well understood, studies have consistently shown that genetic factors explain about half of the variance. It is likely that most cases of PD have a complex genetic basis. Existing data suggest, however, that the genetic architecture underlying PD is heterogeneous and differs between cases. For example, the degree of genetic complexity, and the pattern of genes involved might differ in familial versus non-familial cases, in early- versus late-onset cases, or when different comorbid conditions, gender and potential intermediate or sub-phenotypes are considered. At the molecular genetic level, linkage and associatio... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4869495 Tue, 24 May 2011 23:00:00 +0100 4869495 http://www.medworm.com/index.php?rid=4757705&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F358%3Frss%3D1 Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder caused by mutations in the ACVRL1, ENG, and SMAD4 genes. HHT is commonly characterised by small arteriovenous malformations (AVMs) known as telangiectasias of the skin, oral or gastrointestinal mucosa, as well as larger AVMs of solid organs (lungs, liver, brain). However, the manifestations of HHT are extremely variable. Two patients with no family history of HHT and strikingly different clinical presentations, who are mosaic for mutations in the ACVRL1 or ENG gene, are reported here. These cases represent the first report of mosaicism in patients clinically affected with classical HHT and pulmonary arterial hypertension, and suggest the need for awareness of mosaicism when performing clinical testing for this d... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757705 Tue, 26 Apr 2011 23:00:00 +0100 4757705 http://www.medworm.com/index.php?rid=4757704&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F353%3Frss%3D1 Conclusions The results show the importance of investigating patients without prior family history for the presence of mutational mosaicism, as detecting this would enable appropriate genetic screening and targeted medical care for at-risk children of mosaic patients. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757704 Tue, 26 Apr 2011 23:00:00 +0100 4757704 http://www.medworm.com/index.php?rid=4757703&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F343%3Frss%3D1 Conclusion UNC13D mutations are scattered over the gene. Ethnic-specific mutations were not identified. CNS involvement is more common than in FHL2; in patients with FHL3 and disruptive mutations, age at diagnosis is significantly higher than in FHL2. The combination of fever, splenomegaly, thrombocytopenia and hyperferritinaemia appears to be the most easily and frequently recognised clinical pattern and their association with defective granule release assay may herald FHL3. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757703 Tue, 26 Apr 2011 23:00:00 +0100 4757703 http://www.medworm.com/index.php?rid=4757702&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F334%3Frss%3D1 Conclusion CHARGE syndrome is an extremely variable clinical syndrome. CHD7 analysis can be helpful in the diagnostic process, but the phenotype cannot be predicted from the genotype. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757702 Tue, 26 Apr 2011 23:00:00 +0100 4757702 http://www.medworm.com/index.php?rid=4757701&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F327%3Frss%3D1 Dyskeratosis congenita (DC) is a premature ageing syndrome characterised by short telomeres. An X-linked form of DC is caused by mutations in DKC1 which encodes dyskerin, a telomerase component that is essential for telomerase RNA stability. However, mutations in DKC1 are identifiable in only half of X-linked DC families. A four generation family with pulmonary fibrosis and features of DC was identified. Affected males showed the classic mucocutaneous features of DC and died prematurely from pulmonary fibrosis. Although there were no coding sequence or splicing variants, genome wide linkage analysis of 16 individuals across four generations identified significant linkage at the DKC1 locus, and was accompanied by reduced dyskerin protein levels in affected males. Decreased dyskerin levels w... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757701 Tue, 26 Apr 2011 23:00:00 +0100 4757701 http://www.medworm.com/index.php?rid=4757700&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F323%3Frss%3D1 Conclusions Genotypes and copy number information provided by SNP array allow determination of parental origin and uniparental disomy status and direct quantification of mosaicism. Such information may lead to a better understanding of mechanisms underlying mosaic aneuploidies and the observed phenotypic variability and better prediction of recurrent risk. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757700 Tue, 26 Apr 2011 23:00:00 +0100 4757700 http://www.medworm.com/index.php?rid=4757699&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F317%3Frss%3D1 Conclusions The sequences involved in both the 9q13-q21 duplication and deletion appear the same, implying reciprocity and suggesting non-allelic homologous recombination as the underlying mechanism. All four known euchromatic variants of chromosome 9 have now been shown to encompass segmental duplications. Importantly, a set of validated FISH probes was defined for the detection and characterisation of this 9q13-q21 amplification in the context of other chromosome 9 variants, allowing apparently benign variants to be distinguished from pathogenic changes. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757699 Tue, 26 Apr 2011 23:00:00 +0100 4757699 http://www.medworm.com/index.php?rid=4757698&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F312%3Frss%3D1 Conclusion The smallest duplication is described, which partially overlaps the reported duplications but has a different breakpoint, and its association with BDA2 in a Chinese family is confirmed. The results also provide evidence for cis-regulatory sequences in the duplication 3' of BMP2. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757698 Tue, 26 Apr 2011 23:00:00 +0100 4757698 http://www.medworm.com/index.php?rid=4757697&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F308%3Frss%3D1 Silver–Russell syndrome (SRS) is characterised by prenatal and postnatal growth retardation, dysmorphic facial features, and body asymmetry. In 35–60% of SRS cases the paternally methylated imprinting control region (ICR) upstream of the H19 gene (H19-ICR) is hypomethylated, leading to downregulation of IGF2 and bi-allelic expression of H19. H19 and IGF2 are reciprocally imprinted genes on chromosome 11p15. The expression is regulated by the imprinted methylation of the ICR, which modulates the transcription of H19 and IGF2 facilitated by enhancers downstream of H19. A promoter element of IGF2, IGF2P0, is differentially methylated equivalently to the H19-ICR, though in a small number of SRS cases this association is disrupted—that is, hypomethylation affects either H19-IC... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757697 Tue, 26 Apr 2011 23:00:00 +0100 4757697 http://www.medworm.com/index.php?rid=4757696&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F299%3Frss%3D1 Conclusions Haploinsufficiency of ZFPM2 can cause dominantly inherited isolated diaphragmatic defects with incomplete penetrance. These data define a new minimal deleted region for CDH on 1q41q42, provide evidence for the existence of CDH related genes on chromosomes 16p11.2, 11q23-24 and 13q12, and suggest a possible role for FZD2 and Wnt signalling in pentalogy of Cantrell phenotypes. These results demonstrate the clinical utility of screening for genomic alterations in individuals with both isolated and non-isolated diaphragmatic defects. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757696 Tue, 26 Apr 2011 23:00:00 +0100 4757696 http://www.medworm.com/index.php?rid=4757695&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F290%3Frss%3D1 This article describes seven previously unreported patients with deletions at 2q33.1, all partially overlapping the previously described critical region for the 2q33.1 microdeletion syndrome. The deletions ranged in size from 35 kb to 10.4 Mb, with the smallest deletion entirely within the SATB2 gene. Patients demonstrated significant developmental delay and challenging behaviour, a particular behavioural phenotype that seems to be emerging with more reported patients with this condition. One patient in this cohort has a deletion entirely within SATB2 and has a cleft palate, whereas several patients with larger deletions have a high arched palate. In addition, one other patient has significant orthopaedic problems with ligamentous laxity. Interestingly, this patient has a deletio... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757695 Tue, 26 Apr 2011 23:00:00 +0100 4757695 http://www.medworm.com/index.php?rid=4757694&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F5%2F289%3Frss%3D1 It is difficult to believe how astonishing the idea appeared, only five short years ago, that megabase-scale structural changes in the genome, until then believed to be confined to rare contiguous-gene syndromes, are actually plentiful in phenotypically healthy individuals.1 Routine use of high-resolution array-CGH and, more recently, massively parallel sequencing is revealing a pattern of structural variation in the general population that, in numbers of nucleotides affected, rivals the ubiquitous SNPs. An ever increasing number of pathologies are now associated with copy-number variation on the basis of evidence whose rigour tends to vary among studies. As might be expected, JMG has been receiving increasing numbers of submissions linking copy-number variations to phenotypes and we have ... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4757694 Tue, 26 Apr 2011 23:00:00 +0100 4757694 http://www.medworm.com/index.php?rid=4640338&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F285%3Frss%3D1 Discussion These data suggest that except for TINF2, mutations in shelterin genes are not a common cause of DC. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640338 Fri, 25 Mar 2011 00:00:00 +0100 4640338 http://www.medworm.com/index.php?rid=4640337&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F284%3Frss%3D1 (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640337 Fri, 25 Mar 2011 00:00:00 +0100 4640337 http://www.medworm.com/index.php?rid=4640336&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F279%3Frss%3D1 Conclusion The authors were able to replicate the association between the CRC susceptibility loci on chromosomes 8q23.3 and 11q23 and the risk of developing CRC in patients with Lynch syndrome, but the association could only be detected in MLH1 mutation carriers in this study. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640336 Fri, 25 Mar 2011 00:00:00 +0100 4640336 http://www.medworm.com/index.php?rid=4640335&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F273%3Frss%3D1 Conclusion Constitutional DICER1 haploinsufficiency predisposes to a broad range of tumours, making a substantial contribution to PPB, cystic nephroma and ovarian Sertoli–Leydig tumours, but a smaller contribution to other tumours. Most mutation carriers are unaffected, indicating that tumour risk is modest. The authors define the clinical contexts in which DICER1 mutation testing should be considered, the associated tumour risks, and the implications for at-risk individuals. They have termed this condition ‘DICER1 syndrome’. Accession numbers The cDNA Genbank accession number for the DICER1 sequence reported in this paper is NM_030621.2. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640335 Fri, 25 Mar 2011 00:00:00 +0100 4640335 http://www.medworm.com/index.php?rid=4640334&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F266%3Frss%3D1 Conclusions Contrary to the strong association between UV radiation exposure and melanoma risk for the general population, CDKN2A mutation carriers appear to have the same cumulative risk of melanoma irrespective of the ambient UV irradiance of the region in which they live. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640334 Fri, 25 Mar 2011 00:00:00 +0100 4640334 http://www.medworm.com/index.php?rid=4640333&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F261%3Frss%3D1 This study analysed the cumulative incidence and gender effects as well as the genotype–phenotype correlation between the position of the NF2 mutation and the occurrence of cranial meningiomas in a cohort of 411 NF2 patients with proven NF2 mutations. Results and conclusion Patients with mutations in exon 14 or 15 were least likely to develop meningiomas. Cumulative risk of cranial meningioma to age 50 years was 70% for exons 1–3, 81% for exons 4–6, 49% for exons 7–9, 56% for exons 10–13, and 28% for exons 14–15. In the cohort of 411 patients, no overall gender bias was found for occurrence of meningioma in NF2 disease. Cumulative incidence of meningioma was close to 80% by 70 years of age for both males and females, but incidence by age 20&nb... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640333 Fri, 25 Mar 2011 00:00:00 +0100 4640333 http://www.medworm.com/index.php?rid=4640332&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F256%3Frss%3D1 Conclusion It is possible that genotype is a significant determinant of the risk of development of OPGs in NF1. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640332 Fri, 25 Mar 2011 00:00:00 +0100 4640332 http://www.medworm.com/index.php?rid=4640331&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F251%3Frss%3D1 Conclusion This report demonstrates the power of exome sequencing efficiently applied to a traditional positional cloning pipeline in disease gene discovery, and suggests that the phenotype produced by GJC2 mutations is predominantly one of 4 limb lymphoedema. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640331 Fri, 25 Mar 2011 00:00:00 +0100 4640331 http://www.medworm.com/index.php?rid=4640330&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F242%3Frss%3D1 Conclusions This study proposes a new chromosome fragility index and suggests that genome instability during embryo development may be related to malformations in FA, while DEB-induced chromosome breaks in T cells have no prognostic value for the haematological disease. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640330 Fri, 25 Mar 2011 00:00:00 +0100 4640330 http://www.medworm.com/index.php?rid=4640329&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F235%3Frss%3D1 Conclusions These results show that sequencing of the coding region of CFTR followed by analysis of CFTR transcription could be a useful diagnostic approach to confirm that patients with mild forms of CF harbour deleterious alterations in both CFTR genes. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640329 Fri, 25 Mar 2011 00:00:00 +0100 4640329 http://www.medworm.com/index.php?rid=4640328&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F226%3Frss%3D1 Conclusions This study identified and characterised 21 novel FH mutations and demonstrated that PRCCII can be the only one manifestation of HLRCC. Due to the incomplete penetrance of HLRCC, the authors propose to extend the FH mutation analysis to every patient with PRCCII occurring before 40 years of age or when renal tumour harbours characteristic histologic features, in order to discover previously ignored HLRCC affected families. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640328 Fri, 25 Mar 2011 00:00:00 +0100 4640328 http://www.medworm.com/index.php?rid=4640327&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F219%3Frss%3D1 Conclusion This is the first report of a homozygous BLVRA inactivating mutation indicating that the complete absence of BVRα activity is a non-lethal condition, the most evident phenotypic characteristic of which is the appearance of green jaundice accompanying cholestasis episodes. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640327 Fri, 25 Mar 2011 00:00:00 +0100 4640327 http://www.medworm.com/index.php?rid=4640326&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F4%2F217%3Frss%3D1 (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4640326 Fri, 25 Mar 2011 00:00:00 +0100 4640326 http://www.medworm.com/index.php?rid=4481297&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F216-b%3Frss%3D1 (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481297 Tue, 15 Feb 2011 00:00:00 +0100 4481297 http://www.medworm.com/index.php?rid=4481295&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F212%3Frss%3D1 Molecular studies in a patient with Beckwith–Wiedemann syndrome phenotype who developed two different tumours revealed an unexpected observation of almost complete loss of heterozygosity of all chromosomes. It is shown, by means of numerous molecular methods, that the absence of maternal contribution in somatic cells is due to high-degree (~85%) genome-wide paternal uniparental disomy (UPD). The observations indicate that the genome-wide UPD results from diploidisation, and have important implications for genetic counselling and tumour surveillance for the growing number of UPD associated imprinting disorders. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481295 Tue, 15 Feb 2011 00:00:00 +0100 4481295 http://www.medworm.com/index.php?rid=4481294&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F210%3Frss%3D1 Conclusion These data provide further evidence of the association of MS disease with variation within CBLB. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481294 Tue, 15 Feb 2011 00:00:00 +0100 4481294 http://www.medworm.com/index.php?rid=4481293&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F205%3Frss%3D1 Conclusions This is the first report identifying a genetic defect in CSF2RB that causes deficiency of GM-CSF-Rβc expression and impaired signalling downstream. These results suggested that GM-CSF signalling was compensated by other signalling pathways, leading to adult-onset PAP. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481293 Tue, 15 Feb 2011 00:00:00 +0100 4481293 http://www.medworm.com/index.php?rid=4481292&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F197%3Frss%3D1 Conclusion The finding of microdeletion at 16p11.2 in 2/38 (5%) of isolated and 2/25 (8%) of syndromic cases suggests a significant contribution of this copy number variant alone to the pathogenesis of Müllerian aplasia. Overall, the high incidence of recurrent copy number variants in all forms of Müllerian aplasia has implications for the understanding of the aetiopathogenesis of the condition, and for genetic counselling in families affected by it. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481292 Tue, 15 Feb 2011 00:00:00 +0100 4481292 http://www.medworm.com/index.php?rid=4481291&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F190%3Frss%3D1 Conclusions We found evidence for a polygenic model underlying one of the major traits of OAG, VCDR, and OAG itself. The IOP did not show any evidence for such a model. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481291 Tue, 15 Feb 2011 00:00:00 +0100 4481291 http://www.medworm.com/index.php?rid=4481290&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F183%3Frss%3D1 Conclusion SLSJ-COX is clinically distinct, with acute fatal acidotic crises on a backdrop of chronic moderate developmental delay and hyperlactataemia. Leigh syndrome is common. Stroke-like episodes can occur. The Leigh syndrome of SLSJ-COX differs from that of SURF1-related COX deficiency. SLSJ-COX has a different spectrum of associated abnormalities, acidotic crises being particularly suggestive of LRPPRC related Leigh syndrome. Even among A354V homozygotes, pronounced differences in survival and severity occur, showing that other genetic and/or environmental factors can influence outcome. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481290 Tue, 15 Feb 2011 00:00:00 +0100 4481290 http://www.medworm.com/index.php?rid=4481289&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F177%3Frss%3D1 Conclusions The current report corroborates the previously described unique phenotype of TMEM70 deficiency. The study identifies TMEM70 gene defect as a pan-ethnic disorder and further redefines it as the most common cause of nuclear-origin ATP synthase deficiency. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481289 Tue, 15 Feb 2011 00:00:00 +0100 4481289 http://www.medworm.com/index.php?rid=4481288&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F168%3Frss%3D1 Conclusion This 39 year follow-up study of XP patients indicates a major role of DNA repair genes in the aetiology of skin cancer and neurologic degeneration. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481288 Tue, 15 Feb 2011 00:00:00 +0100 4481288 http://www.medworm.com/index.php?rid=4481287&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F160%3Frss%3D1 Discussion and conclusion Why these specific arginine and glycine substitutions cause the inversa distribution remains unknown. It was not possible to identify clear differences in location and nature of substituting amino acids between these mutations and missense mutations causing other RDEB phenotypes. It is hypothesised that the higher skin temperature in the affected areas plays an important role in the pathophysiology of RDEB-I. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481287 Tue, 15 Feb 2011 00:00:00 +0100 4481287 http://www.medworm.com/index.php?rid=4481286&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F152%3Frss%3D1 Conclusions As the vas deferens seems to be one of the tissues most susceptible to a reduction in the normal CFTR transcripts levels, and as two mild mutations are sufficient to induce CBAVD phenotype, these findings raise the possibility that these uncommon variants may be a novel cause of CBAVD. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481286 Tue, 15 Feb 2011 00:00:00 +0100 4481286 http://www.medworm.com/index.php?rid=4481285&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F3%2F145%3Frss%3D1 Background The genetic heterogeneity of many Mendelian disorders, such as retinitis pigmentosa which results from mutations in over 40 genes, is a major obstacle to obtaining a molecular diagnosis in clinical practice. Targeted high-throughput DNA sequencing offers a potential solution and was used to develop a molecular diagnostic screen for patients with retinitis pigmentosa. Methods A custom sequence capture array was designed to target the coding regions of all known retinitis pigmentosa genes and used to enrich these sequences from DNA samples of five patients. Enriched DNA was subjected to high-throughput sequencing singly or in pools, and sequence variants were identified by alignment of up to 10 million reads per sample to the normal reference sequence. Potential pathogenicity was... Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4481285 Tue, 15 Feb 2011 00:00:00 +0100 4481285 http://www.medworm.com/index.php?rid=4404293&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F2%2F141%3Frss%3D1 Conclusion These findings, along with previous reports of human and mouse mutations in other members of the complex, indicate that disruption of any one of the four subunits of AP-4 causes dysfunction of the entire complex, leading to a distinct ‘AP-4 deficiency syndrome’. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4404293 Thu, 27 Jan 2011 00:00:00 +0100 4404293 http://www.medworm.com/index.php?rid=4404292&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F2%2F140%3Frss%3D1 (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4404292 Thu, 27 Jan 2011 00:00:00 +0100 4404292 http://www.medworm.com/index.php?rid=4404291&cid=s_33040_50_f&fid=33040&url=http%3A%2F%2Fjmg.bmj.com%2Fcgi%2Fcontent%2Fshort%2F48%2F2%2F136%3Frss%3D1 Conclusion Genome-wide CNV screening with high density arrays provides a tool to detect intragenic deletions in the COH1 gene. This report presents an example of how microarrays can be used to identify autosomal recessive syndromes and to extend the phenotypic and mutational spectrum of recessive disorders. (Source: Journal of Medical Genetics) Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4404291 Thu, 27 Jan 2011 00:00:00 +0100 4404291