Friedman E, Gordeladze J O, Gejman P V, Murtagh J J, Gertch D S, Tu T
Molecular Pathophysiology Branch, National Institute of Digestive, Diabetes, and Kidney Disease, NIH, Bethesda, Maryland.
Basic Res Cardiol. 1992 Mar-Apr;87(2):106-12. doi: 10.1007/BF00801958.
Familial hypertrophic cardiomyopathy (FHCM) has been linked to the cardiac beta-myosin heavy-chain (MHC) genes on chromosome 14 (14q1), and a missense mutation within exon 13 of the beta MHC gene has been implicated in the pathogenesis of the disease. To test whether this constitutional mutation occurs somatically in the myocardium of the sporadic form of the disease, we studied seven patients with familial (n = 3) or sporadic (n = 4) hypertrophic cardiomyopathy (HCM). Amplification of exon 13 of the beta MHC from paraffin-embedded myocardium using the polymerase chain reaction (PCR) was performed and analysis of the amplified product for migration abnormalities using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of the PCR product were used. Neither patients with HCM nor subjects with dilated cardiomyopathy (DCM) (n = 2) exhibited an aberration within exon 13 of the myocardial beta MHC. It is concluded that a specific beta MHC gene mutation is displayed only in a subset of patients with familial disease, thus further emphasizing the notion of genetic heterogeneity. In addition, in the sporadic form of the disease, somatically occurring mutations in this particular exon could not be demonstrated.
家族性肥厚型心肌病（FHCM）与位于14号染色体（14q1）上的心脏β-肌球蛋白重链（MHC）基因有关，β-MHC基因第13外显子内的一个错义突变被认为与该病的发病机制有关。为了检测这种构成性突变是否在散发性疾病的心肌中体细胞发生，我们研究了7例家族性（n = 3）或散发性（n = 4）肥厚型心肌病（HCM）患者。使用聚合酶链反应（PCR）从石蜡包埋的心肌中扩增β-MHC的第13外显子，并使用变性梯度凝胶电泳（DGGE）分析扩增产物的迁移异常情况，同时对PCR产物进行直接测序。肥厚型心肌病患者和扩张型心肌病（DCM）患者（n = 2）在心肌β-MHC的第13外显子内均未表现出异常。结论是，特定的β-MHC基因突变仅在一部分家族性疾病患者中出现，从而进一步强调了遗传异质性的概念。此外，在散发性疾病中，未能证明该特定外显子存在体细胞发生的突变。
