Hypertrophic cardiomyopathy is an autosomal-dominant disease.Disease-causing mutations have been found in genes encoding structural components of the thick and thin filament systems of cardiac myocyte;it has therefore been named as a disease of sarcomere.Many approaches have been used to characterize the pathogenesis of the desease.Transgenic animal models have been created to gain further insight into the pathogenesis of this disease.Most of these models has been made in mice;however,recently a transgenic rabbit model has been created.In addition,there are several natural-occurring forms of HCM in animals.The discovery of responsible genes and the elucidation of the molecular mechanisms of pathogenesis through the use of animal models promise improved and early diagnosis and the potential for mechanism-based therapeutics.
目的研究国人肥厚型心肌病（HCM）患者的致病基因～肌球蛋白结合蛋白c基因（myosin binding protein C gene，MYBPC3）的突变位点，分析基因突变类型与临床表型的相互关系。方法对66例HCM患者的MYBPC3基因进行扫描，聚合酶链反应扩增其外显子及剪接部位的基因组DNA片段，直接测序分析。分析各突变患者相应的临床表型特点。结果经测序分析，发现Lys301fs移码突变、Asp463stop无义突变、Gly523Arg错义突变和Tyr847His错义突变。MYBPC3导致的HCM为3例，占病例总数的4．5％。其临床表型各异，患者H30（Lys301fs）47岁发病，活动后胸闷、气短，超声显示室间隔肥厚达18．7mm，左心室后壁14．7mm。患者H48（Asp463stop）为25岁男性，24岁发病，室间隔肥厚达15．4mm。患者H53（Gly523Arg和Tyr847His）发病年龄36岁，活动后胸闷、憋气，伴心前区疼痛，室间隔肥厚达27mm。结论MYBPC3突变为HCM主要致病原因之一。MYBPC3突变基因携带者临床表型差异大。国人MYBPC3突变患者多在青壮年期发病，不同于国外报道的多发病较晚。
