Bmc Med Genet
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Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and neurophysiological data gathered under ideal conditions for clinical assessment. However, in a diagnostic laboratory setting relying on external test requisitions and patient samples, such conditions are not always met. Our objective was therefore to perform a retrospective evaluation of the data given in laboratory request forms and to assess their quality and applicability with regard to the recommended algorithms for CMT diagnostics. As we are the main test centre for CMT in Norway our results also provide an overview of the spectrum of gene defects in the Norwegian CMT population. ⋯ We suggest a simplified algorithm intended for referral centres, dealing with DNA/blood samples, which involves the assessment of age at onset and neurophysiological data followed by testing of four genes; PMP22 (duplication), MPZ, GJB1 and MFN2. Patients negative for mutations in those four genes should be subjected to evaluation at an interdisciplinary inherited neuropathy clinic with the capacity for extended molecular genetic analysis by next generation sequencing.
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The triallelic serotonin transporter gene linked polymorphic region (5-HTTLPR) has been associated with alterations in thermal pain perception. The primary aim of this study was to investigate the associations between heat pain (HP) perception and the triallelic 5-HTTLPR in a large cohort of adults with chronic pain. ⋯ In this study that involved adults with chronic pain, the intermediate triallelic 5-HTTLPR expressing group, but not the low expressing group, was associated with greater HP thresholds compared to the high expressing group.
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Interleukin (IL)-18, an important proinflammatory cytokine, plays a potential pathological role in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Studies on the relationship of IL-18 gene promoter rs1946518 (-607A/C) polymorphism, rs187238 (-137G/C) polymorphism with RA and SLE are inconclusive. The aim of this study was to get a more precise estimation of the relationship in Asian populations. ⋯ This meta-analysis indicates that the IL-18-607A/C polymorphism may confer susceptibility to RA and SLE in Chinese population, but not all Asians.
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Hypertrophic Cardiomyopathy (HCM) is a genetically heterogeneous disease. One specific mutation in the MYBPC3 gene is highly prevalent in center east of France giving an opportunity to define the clinical profile of this specific mutation. ⋯ A founder mutation arising at about the 10th century in the MYBPC3 gene accounts for 8.4% of all HCM in center east France and results in a cardiomyopathy starting late and evolving slowly but with an apparent risk of sudden death similar to other sarcomeric mutations.
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Germline mutations of BRCA1/2 are associated with hereditary breast and ovarian cancer. Recent data suggests excess mortality in mutation carriers beyond that conferred by neoplasia, and recent in vivo and in vitro studies suggest a modulatory role for BRCA proteins in endothelial and cardiomyocyte function. We therefore tested the association of BRCA2 variants with clinical cardiovascular disease (CVD). ⋯ Although there was an association between two SNPs in BRCA2 and CVD in a multi-ethnic population, these results were not replicated in two South Asian case-control studies of incident MI. Future studies exploring the association between BRCA variants and cardiovascular disorders are needed to clarify the role, if any, for BRCA variants in CVD pathogenesis.