Sporadic hypertrophic cardiomyopathy due to de novo myosin mutations.
Sporadic hypertrophic cardiomyopathy due to de novo myosin mutations.
复制标题
由于肌球蛋白新生突变导致散发性肥厚型心肌病。
DOI：
10.1172/jci116038
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Seidman,CE
中科院分区：
文献类型：
--
作者：
Watkins,H;Thierfelder,L;Hwang,DS;McKenna,W;Seidman,JG;Seidman,CE
肥厚型心肌病是一种常染色体显性遗传的家族性疾病，也可以是一种无家族史的散发性疾病。虽然β心肌肌球蛋白重链（MHC）基因的错义突变占所有家族性肥厚型心肌病病例的大约一半，但散发性肥厚型心肌病的分子原因尚不清楚。为了确定β心脏MHC突变是否也与散发性疾病相关，我们在7名散发性肥厚型心肌病患者中筛选了该基因。在两个散发性疾病的先证者中发现了β心脏MHC基因突变。在他们的父母既没有临床上也没有遗传影响，我们得出结论，在每个先证者的突变出现从头。突变和疾病传播给后代发生在一个家系中，预测这些是种系突变。在一个家系中发生的肥厚性心肌病与从头突变的出现相一致的证明提供了令人信服的遗传证据，即β心脏MHC突变导致这种疾病。我们认为，新发突变占一些情况下，散发性肥厚型心肌病，这些突变可以传递给儿童。确定家族性肥厚型心肌病基因突变的临床益处也适用于一些散发性疾病患者。图片
Hypertrophic cardiomyopathy occurs as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. While missense mutations in the beta cardiac myosin heavy chain (MHC) gene account for approximately half of all cases of familial hypertrophic cardiomyopathy, the molecular causes of sporadic hypertrophic cardiomyopathy are unknown. To determine whether beta cardiac MHC mutations are also associated with sporadic disease, we screened this gene in seven individuals with sporadic hypertrophic cardiomyopathy. Mutations in the beta cardiac MHC genes were identified in two probands with sporadic disease. In that their parents were neither clinically nor genetically affected, we conclude that mutations in each proband arose de novo. Transmission of the mutation and disease to an offspring occurred in one pedigree, predicting that these are germline mutations. The demonstration of hypertrophic cardiomyopathy arising within a pedigree coincident with the appearance of a de novo mutation provides compelling genetic evidence that beta cardiac MHC mutations cause this disease. We suggest that de novo mutations account for some instances of sporadic hypertrophic cardiomyopathy and that these mutations can be transmitted to children. The clinical benefits of defining mutations responsible for familial hypertrophic cardiomyopathy should also be available to some patients with sporadic disease.Images
登录
查看更多内容
影响因子：
2.8
作者：
MARON, BJ;NICHOLS, PF;MULVIHILL, JJ
通讯作者：
MULVIHILL, JJ
影响因子：
2.8
作者：
MARON, BJ;GOTTDIENER, JS;EPSTEIN, SE
通讯作者：
EPSTEIN, SE
D1S103 基因座的二核苷酸重复多态性。
影响因子：
14.9
作者：
Weber,JL;Kwitek,AE;May,PE
通讯作者：
May,PE
患有梗阻性心肌病（不对称肥厚）的家庭
影响因子：
--
作者：
A. Hollman;J. Goodwin;D. Teare;J. Renwick
通讯作者：
J. Renwick
D21S172 基因座的二核苷酸重复多态性。
影响因子：
14.9
作者：
V. Sharma;L. Allen;R. Magenis;M. Litt
通讯作者：
M. Litt