Arai S, Matsuoka R, Hirayama K, Sakurai H, Tamura M, Ozawa T, Kimura M, Imamura S, Furutani Y, Joh-o K
Heart Institute of Japan, Tokyo, Japan.
Am J Med Genet. 1995 Sep 11;58(3):267-76. doi: 10.1002/ajmg.1320580314.
Hypertrophic cardiomyopathy occurs as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. We describe a missense mutation of the beta-cardiac myosin heavy chain (MHC) gene, a G to T transversion (741 Gly-->Trp) identified by direct sequencing of exon 20 in four individuals affected with familial hypertrophic cardiomyopathy. Three individuals with sporadic hypertrophic cardiomyopathy, whose parents are clinically and genetically unaffected, had sequence variations of exon 34 of the alpha-cardiac MHC gene (a C to T transversion, 1658 Asp-->Asp, resulting in FokI site polymorphism), of intron 33 of the alpha-cardiac MHC gene (a G to A and an A to T transversion), and also of intron 14 of the beta-cardiac MHC gene (a C to T transversion in a patient with Noonan syndrome). Including our case, 30 missense mutations of the beta-cardiac MHC gene in 49 families have been reported thus far worldwide. Almost all are located in the region of the gene coding for the globular head of the molecule, and only one mutation was found in both Caucasian and Japanese families. Missense mutations of the beta-cardiac MHC gene in hypertrophic cardiomyopathy may therefore differ according to race.
肥厚型心肌病可作为常染色体显性遗传病出现，也可作为无家族遗传史的散发性疾病出现。我们描述了β-心脏肌球蛋白重链（MHC）基因的一个错义突变，即通过对4名家族性肥厚型心肌病患者的第20外显子进行直接测序鉴定出的G到T的颠换（741 Gly→Trp）。3名散发性肥厚型心肌病患者，其父母在临床和基因方面均未受影响，他们的α-心脏MHC基因第34外显子存在序列变异（C到T的颠换，1658 Asp→Asp，导致FokI位点多态性）、α-心脏MHC基因第33内含子存在序列变异（G到A和A到T的颠换），以及β-心脏MHC基因第14内含子存在序列变异（一名努南综合征患者中C到T的颠换）。包括我们的病例在内，迄今为止全球已报道49个家族中β-心脏MHC基因有30个错义突变。几乎所有突变都位于该基因编码分子球状头部的区域，且仅在白种人和日裔家族中发现了一个相同的突变。因此，肥厚型心肌病中β-心脏MHC基因的错义突变可能因种族而异。
