A MOLECULAR-BASIS FOR FAMILIAL HYPERTROPHIC CARDIOMYOPATHY - A BETA-CARDIAC MYOSIN HEAVY-CHAIN GENE MISSENSE MUTATION
A MOLECULAR-BASIS FOR FAMILIAL HYPERTROPHIC CARDIOMYOPATHY - A BETA-CARDIAC MYOSIN HEAVY-CHAIN GENE MISSENSE MUTATION
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DOI：
10.1016/0092-8674(90)90274-i
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发表时间：
1990-09-07
期刊：
影响因子：
64.5
通讯作者：
SEIDMAN, JG
中科院分区：
文献类型：
--
作者：
GEISTERFERLOWRANCE, AAT;KASS, S;SEIDMAN, JG
在一个大家族的所有患有家族性肥厚型心肌病（FHC）的个体中，β心肌肌球蛋白重链（MHC）基因第13外显子存在一个点突变。这种错义突变将一个高度保守的精氨酸残基（Arg - 403）转变为谷氨酰胺。来自一个无亲缘关系家庭的患病个体没有这种错义突变，而是有一个α/β心肌MHC杂合基因。在两个无亲缘关系家庭的所有FHC个体中，在心肌MHC基因内鉴定出两种独特的突变，这表明心肌MHC基因的缺陷可导致这种疾病。由403位残基的错义突变导致的病理情况进一步表明，这种突变破坏了肌球蛋白的一项关键功能。
A point mutation in exon 13 of the .beta. cardiac myosin heavy chain (MHC) gene is present in all individuals affected with familial hypertrophic cardiomyopathy (FHC) from a large kindred. This missense mutation converts a highly conserved arginine residue (Arg-403) to a glutamine. Affected individuals from an unrelated family lack this missense mutation, but instead have an .alpha./.beta. cardiac MHC hybrid gene. Identification of two unique mutations within cardiac MHC genes in all individuals with FHC from two unrelated families demonstrates that defects in the cardiac MHC genes can cause this disease. The pathology resulting from a missense mutation at residue 403 further suggests that a critical function of myosin is disrupted by this mutation.