Nishi H, Kimura A, Harada H, Adachi K, Koga Y, Sasazuki T, Toshima H
Third Department of Internal Medicine, Kurume University, School of Medicine, Japan.
Biochem Biophys Res Commun. 1994 Apr 15;200(1):549-56. doi: 10.1006/bbrc.1994.1483.
We have examined for a mutation in the cardiac beta myosin heavy chain gene from Japanese patients with familial hypertrophic cardiomyopathy. A missense mutation due to a G to A transition in codon 935, leading to a replacement of Glu with Lys, was found in one patient. Family members of this patient were then examined. It was revealed that both the proband and his elder brother, who was also a symptomatic patient, were homozygous for the mutation. The proband eventually died of intractable heart failure, and his brother died suddenly in their thirties. On the other hand, his parents, who were first cousins and heterozygous for the mutation, had cardiac hypertrophy without clinical symptoms. His elder sister was also heterozygous for the mutation, however, she did not manifest with cardiac hypertrophy. These observations suggest a gene-dose-like effect of the mutant cardiac beta myosin heavy chain gene on the clinical manifestation of familial hypertrophic cardiomyopathy.
我们检测了日本家族性肥厚型心肌病患者心脏β肌球蛋白重链基因的突变情况。在一名患者中发现了由于密码子935处的G到A转换导致的错义突变，该突变导致谷氨酸被赖氨酸取代。随后对该患者的家庭成员进行了检测。结果显示，先证者及其同样有症状的哥哥均为该突变的纯合子。先证者最终死于难治性心力衰竭，其哥哥在三十多岁时突然死亡。另一方面，他的父母是近亲，为该突变的杂合子，有心脏肥厚但无临床症状。他的姐姐也是该突变的杂合子，然而，她并未表现出心脏肥厚。这些观察结果提示突变的心脏β肌球蛋白重链基因对家族性肥厚型心肌病的临床表现存在基因剂量样效应。
