Two novel mutations in the β-myosin heavy chain gene associated with dilated cardiomyopathy
Two novel mutations in the β-myosin heavy chain gene associated with dilated cardiomyopathy
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DOI：
10.1016/j.ejheart.2004.04.017
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发表时间：
2004-12-01
影响因子：
18.2
通讯作者：
Peuhkurinen, K
中科院分区：
文献类型：
--
作者：
Kärkkäinen, S;Heliö, T;Peuhkurinen, K
背景：扩张性心脏病（DCM）是家族性的，约20-35%的特发性DCM病例。已经报道了不同肌节蛋白基因中的几种突变引起DCM。目的：我们想研究肌节蛋白基因变异在芬兰扩张型心肌病患者中的作用。方法与结果：我们通过PCR-SSCP和测序方法筛选了芬兰东部52例DCM患者中5个肌节蛋白基因（β-肌球蛋白重链、α-原肌球蛋白、肌钙蛋白C、肌钙蛋白I和肌钙蛋白T）的所有编码外显子。两个新的突变，Arg 1053 Gln和Arg 1500 Trp，在β-肌球蛋白重链基因在两个索引患者被检测到。先证者与Argl 053 Gln突变有左心室扩张和收缩功能受损，但其他家庭成员携带这种突变提出了室间隔肥大。因此，似乎Arg 1053 Gln突变主要是HCM突变，其也可导致DCM。另一个突变Argl 500 Trp与典型的DCM表型相关。Argl 500 Trp突变携带者只有一个家庭成员活着，但她没有携带突变，因此，在这个家庭中的突变和疾病的共分离不能得到可靠的验证。在其他肌节蛋白基因中未发现致病突变。结论：在DCM患者中检测到两种新的β-肌球蛋白重链基因突变。总的来说，在芬兰扩张型心肌病患者中，肌球蛋白重链基因突变似乎相对少见。(C)2004年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Background: Dilated cardiomopathy (DCM) is familial in approximately 20-35% of cases of idiopathic DCM. Several mutations in the different sarcomere protein genes have been reported to cause DCM. Aims: We wanted to investigate the role of sarcomere protein gene variants in Finnish DCM patients. Methods and results: We screened all coding exons of five sarcomere protein genes (beta-myosin heavy chain, alpha-tropomyosin, troponin C, troponin I and troponin T) in a well-characterized population of 52 DCM patients in Eastern Finland by the PCR-SSCP and sequencing method. Two novel mutations, Arg1053Gln and Arg1500Trp, in the beta-myosin heavy chain gene in two index patients were detected. The proband with the Argl053Gln mutation had a dilated left ventricle and impaired systolic function, but other family members carrying this mutation presented with septal hypertrophy. It thus seems that the Argl053Gln mutation is primarily a HCM mutation, which can also lead to DCM. The other mutation, Argl500Trp, was associated with a typical DCM phenotype. The Argl500Trp mutation carrier had only one family member alive, but she did not carry the mutation and, therefore, cosegregation of the mutation and the disease in this family could not be reliably verified. No disease-causing mutations were found in the other sarcomere protein genes. Conclusions: Two novel mutations in the beta-myosin heavy chain gene were detected in patients with DCM. Overall, mutations in the Pmyosin heavy chain gene seem to be relatively uncommon in Finnish DCM patients. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.