Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden
Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden
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DOI：
10.1016/s0022-2828(03)00146-9
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发表时间：
2003-07-01
影响因子：
5
通讯作者：
Waldenström, A
中科院分区：
文献类型：
--
作者：
Mörner, S;Richard, P;Waldenström, A
肥厚型心肌病（HCM）是一种异质性疾病，具有可变的基因型和表型表达，通常由肌节蛋白基因突变引起。本研究的目的是确定在瑞典北方与HCM相关的基因型和相关表型。在46例家族性或散发性肥厚型心肌病的无关个体中，进行了8个肌节蛋白基因的突变分析：心肌β-肌球蛋白重链、心肌肌球蛋白结合蛋白C、心肌肌钙蛋白T、α-原肌球蛋白、心肌必需和调节肌球蛋白轻链、心肌肌钙蛋白I和心肌α-肌动蛋白。在13个个体中共发现11个突变，其中6个是新的突变。七个突变位于肌球蛋白结合蛋白C基因，两个在β-肌球蛋白重链基因和一个在调节肌球蛋白轻链和肌钙蛋白I基因，分别。这是瑞典的第一项研究，对HCM人群进行了基因分型。心肌肌球蛋白结合蛋白C基因突变是瑞典北方最常见的突变，而β-肌球蛋白重链基因突变的频率低于以前的描述。这些基因介导的表型存在差异，其特征在于肌球蛋白结合蛋白C基因突变的迟发性疾病。在评估疾病诊断中的临床表现时，尤其是在HCM家族中的年轻人中，应考虑到这一点，在肌球蛋白结合蛋白C基因突变的情况下，预计HCM的发病率可能不完全。(C)2003爱思唯尔科技有限公司版权所有。
Hypertrophic cardiomyopathy (HCM) is a heterogenous disease, with variable genotypic and phenotypic expressions, often caused by mutations in sarcomeric protein genes. The aim of this study was to identify the genotypes and associated phenotypes related to HCM in northern Sweden. In 46 unrelated individuals with familial or sporadic HCM, mutation analysis of eight sarcomeric protein genes was performed; the cardiac beta-myosin heavy chain, cardiac myosin-binding protein C, cardiac troponin T, alpha-tropomyosin, cardiac essential and regulatory myosin light chains, cardiac troponin I and cardiac alpha-actin. A total of 11 mutations, of which six were novel ones, were found in 13 individuals. Seven mutations were located in the myosin-binding protein C gene, two in the beta-myosin heavy chain gene and one in the regulatory myosin light chain and troponin I genes, respectively. This is the first Swedish study, where a population with HCM has been genotyped. Mutations in the cardiac myosin-binding protein C gene were the most common ones found in northern Sweden, whereas mutations in the beta-myosin heavy chain gene were less frequent than previously described. There are differences in the phenotypes mediated by these genes characterised by a more late-onset disease for the myosin-binding protein C gene mutations. This should be taken into consideration, when evaluating clinical findings in the diagnosis of the disease, especially in young adults in families with HCM, where penetrance can be expected to be incomplete in the presence of a myosin-binding protein C gene mutation. (C) 2003 Elsevier Science Ltd. All rights reserved.