Harada H, Kimura A, Nishi H, Sasazuki T, Toshima H
Third Department of Internal Medicine, Kurume University, School of Medicine, Japan.
Biochem Biophys Res Commun. 1993 Jul 30;194(2):791-8. doi: 10.1006/bbrc.1993.1891.
A novel missense mutation of the cardiac beta-myosin heavy chain gene was detected in five unrelated Japanese patients and their affected family members with hypertrophic cardiomyopathy (HCM) by using the polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis. Sequencing analysis revealed an A to G transition at codon 778 leading to replacement of the Asp residue, which is adjacent to the interaction sites of myosin heavy chain (MHC) with actin and is a conserved amino acid residue in various MHC across species, to the Gly residue. Linkage study of the mutation and two dinucleotides repeat markers of the cardiac beta-MHC gene in three affected families showed that the mutation was on the same haplotype of the cardiac beta-MHC gene and linked to HCM. These observations strongly suggest that the 778Asp to Gly mutation is the cause of HCM in these affected individuals.
通过聚合酶链反应（PCR）-DNA构象多态性（DCP）分析，在5名无亲缘关系的日本肥厚型心肌病（HCM）患者及其患病家庭成员中检测到心脏β-肌球蛋白重链基因的一种新型错义突变。测序分析显示，密码子778处发生A到G的转换，导致与肌球蛋白重链（MHC）与肌动蛋白相互作用位点相邻且在不同物种的各种MHC中保守的天冬氨酸残基被甘氨酸残基取代。对3个患病家族中该突变与心脏β-MHC基因的两个二核苷酸重复标记进行连锁研究，结果表明该突变位于心脏β-MHC基因的同一单倍型上，并与HCM相关。这些观察结果强烈提示，778位天冬氨酸到甘氨酸的突变是这些患病个体发生HCM的原因。
