Sarcomeric genotyping in hypertrophic cardiomyopathy
Sarcomeric genotyping in hypertrophic cardiomyopathy
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DOI：
10.4065/80.4.463
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发表时间：
2005-04-01
影响因子：
8.9
通讯作者：
Ackerman, MJ
中科院分区：
文献类型：
--
作者：
Van Driest, SL;Ommen, SR;Ackerman, MJ
目的：收集肥厚型心肌病(HCM)患者的研究结果，以阐明重要的表型差异。材料和方法：收集1998年11月至2004年11月发表的数据，并比较来自梅奥诊所(明尼苏达州罗切斯特)、哈佛医学院(波士顿，马萨诸塞州)、法国、德国、瑞典、芬兰和西班牙的无关研究人群的基因分型研究。结果：法国研究人群的突变频率最高(61%)，其次是梅奥诊所(38%)、哈佛医学院(36%)和瑞典研究人群(30%)。对于每个研究人群，肌球蛋白结合蛋白C(MYBPC3)的突变是肥厚性心肌梗死最常见的原因。有肥厚型心肌炎家族史的患者发生突变的频率高于无家族史者。这一合并分析显示，在所有基因型别中，左室壁厚度或平均诊断年龄没有统计学上的差异。结论：根据目前报道的表型数据，肌瘤基因型别，如MYBPC3-HCM和MYH7-HCM，是不可能区分的。除了主要的致病遗传底物之外，无数的遗传和/或环境修饰物在确定患者的特定表型方面必须发挥重要作用。
OBJECTIVE: To pool results from studies of patients with hypertrophic cardiomyopathy (HCM) to elucidate important phenotypic differences among genotypes.MATERIAL AND METHODS: Data published from November 1998 through November 2004 were gathered and compared from unrelated study population genotyping studies from the Mayo Clinic (Rochester, Minn), Harvard Medical School (Boston, Mass), France, Germany, Sweden, Finland, and Spain. Standard statistical analysis techniques were used to pool and compare data across genotypes with respect to frequency of mutations, age at diagnosis, and degree of hypertrophy (left ventricular wall thickness).RESULTS: The French study population harbored the highest frequency of mutations (61%), followed by the Mayo Clinic (38%), Harvard Medical School (36%), and Swedish (30%) study populations. For every study population, mutations in myosin binding protein C (MYBPC3) were the most common cause of HCM. Patients with a family history of HCM had mutations more frequently than those without. This pooled analysis revealed no statistically significant differences in left ventricular wall thickness or in mean age at diagnosis across all genotypes.CONCLUSIONS: Differentiation of sarcomeric genotypes, such as MYBPC3-HCM and MYH7-HCM, is not possible on the basis of currently reported phenotypic data. A myriad of genetic and/or environmental modifiers in addition to the primary disease-causing genetic substrate must play an important role in determining a patient's particular phenotype.