Vosberg H P
Max-Planck-Institut für physiologische und klinische Forschung, Abteilung Experimentielle Kardiologie, Bad Nauheim.
Herz. 1994 Apr;19(2):75-83.
Hypertrophic cardiomyopathy (HCM) can be an inherited disorder. Typically, the inheritance is dominant and genetic cases account for about 50% of all patients with this pathology. Four different HCM loci have been mapped to different chromosomes (no. 1, 11, 14 and 15), yet, only one responsible gene has been identified. It is the beta myosin heavy chain gene on chromosome 14, which is expressed in ventricles and in slow skeletal muscle fibers. A large number of missense mutations has been reported which are predominantly located in the globular head region of the beta myosin. An apparent hot spot of mutation has been detected within exon 13 of the gene, corresponding to amino acid position 403. Although the functional consequences of the various mutations for the activity of beta myosin are not known, by inference and on the basis of published data, it may be suggested that a mutation in position 403 affects the myosin-actin dissociation in the contractile cycle. Despite our knowledge of mutations in the myosin gene, and of many of the pathological sequelas, there still is insufficient information which precludes unequivocal conclusions on the molecular mechanisms by which the pathogenesis of the myosin deficient heart develops. Molecular biology and genetics should help to define the determinants of this disease.
肥厚型心肌病（HCM）可能是一种遗传性疾病。通常，其遗传方式为显性遗传，遗传病例约占所有该病理患者的50%。四个不同的HCM基因座已被定位到不同的染色体上（第1、11、14和15号染色体），然而，仅鉴定出一个致病基因。它是位于14号染色体上的β肌球蛋白重链基因，在心室和慢肌纤维中表达。已报道了大量错义突变，这些突变主要位于β肌球蛋白的球状头部区域。在该基因的第13外显子内检测到一个明显的突变热点，对应于氨基酸位置403。尽管各种突变对β肌球蛋白活性的功能后果尚不清楚，但根据推断并基于已发表的数据，可能提示403位的突变会影响收缩周期中肌球蛋白与肌动蛋白的解离。尽管我们了解肌球蛋白基因中的突变以及许多病理后遗症，但仍然缺乏足够的信息，无法就肌球蛋白缺陷型心脏发病机制的分子机制得出明确结论。分子生物学和遗传学应有助于确定这种疾病的决定因素。
