Detection of a large duplication mutation in the myosin-binding protein C3 gene in a case of hypertrophic cardiomyopathy |
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Authors: | Thomas Meyer Sabine Pankuweit Anette Richter Bernhard Maisch Volker Ruppert |
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Institution: | 1. Department of Psychosomatic Medicine and Psychotherapy, Georg August University of Göttingen, Germany;2. Department of Cardiology, Philipps University of Marburg, Marburg, and University Hospital Gießen–Marburg, Germany |
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Abstract: | Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with autosomal dominant inheritance caused by mutations in genes coding for sarcomeric and/or regulatory proteins expressed in cardiomyocytes. In a small cohort of HCM patients (n = 8), we searched for mutations in the two most common genes responsible for HCM and found four missense mutations in the MYH7 gene encoding cardiac β-myosin heavy chain (R204H, M493V, R719W, and R870H) and three mutations in the myosin-binding protein C3 gene (MYBPC3) including one missense (A848V) and two frameshift mutations (c.3713delTG and c.702ins26bp). The c.702ins26bp insertion resulted from the duplication of a 26-bp fragment in a 54-year-old female HCM patient presenting with clinical signs of heart failure due to diastolic dysfunction. Although such large duplications (> 10 bp) in the MYBPC3 gene are very rare and have been identified only in 4 families reported so far, the identical duplication mutation was found earlier in a Dutch patient, demonstrating that it may constitute a hitherto unknown founder mutation in central European populations. This observation underscores the significance of insertions into the coding sequence of the MYBPC3 gene for the development and pathogenesis of HCM. |
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Keywords: | bp base pair DNA deoxyribonucleic acid dNTP deoxynucleotide EDTA ethylenediaminetetraacetic acid HCM hypertrophic cardiomyopathy Hg mercury LMM light meromyosin domain LV left ventricle LVEDD left ventricular end&mdash diastolic diameter MYBPC3 myosin-binding protein C3 MYH7 cardiac β-myosin heavy chain PCR polymerase chain reaction SAM systolic anterior motion TNNT2 troponin t |
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