Sarcomeric hypertrophic cardiomyopathy: Genetic profile in a Portuguese population
Sarcomeric hypertrophic cardiomyopathy: Genetic profile in a Portuguese population
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DOI：
10.1016/j.repc.2011.12.020
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发表时间：
2012-09-01
影响因子：
1.8
通讯作者：
Madeira, Hugo
中科院分区：
文献类型：
--
作者：
Brito, Dulce;Miltenberger-Miltenyi, Gabriel;Madeira, Hugo
背景：肌节肥厚型心肌病具有异质性表型表现，其中最令人担心的是心源性猝死。基因诊断对于识别每个家庭中存在风险的受试者至关重要。葡萄牙人群中的致病突变谱尚不清楚。方法：通过 PCR 和五个肌节基因（MYBPC3、MYH7、TNNT2、TNNI3 和 MYL2）的测序对 77 名不相关的肥厚型心肌病先证者进行了系统突变筛查。对大多数患者进行了家族共分离分析。结果：在 41 名 (53%) 指标患者中发现了 34 种不同的突变，其中 71% 患有家族性肥厚型心肌病。最常涉及的基因是 MYBPC3 (66%)，在 27 名患者中有 22 种不同的突变（其中 8 种是新突变），其次是 MYH7 (22%)、TNNT2 (12%) 和 TNNI3 (2.6%)。在三名患者 (7%) 中，在 MYBPC3 和/或 MYH7 中发现了两种突变。此外，还对 276 名亲属进行了筛查，从而确定了每个家系中患有该疾病家族形式的其他 3 个受影响亲属的平均值。结论：疾病相关突变主要在家族性肥厚性心肌病中被发现，证实了很少研究的基因可能与散发形式有关的观点。私人突变是规则，MYBPC3 是最常涉及的基因。 MYBPC3 和 MYH7 突变导致大多数肌节相关疾病病例。这些基因可能会发生多种突变，这凸显了筛查这两种基因的重要性。新突变的检测强烈表明应该系统地筛选所有编码区。肥厚型心肌病的基因分型可以更精确地诊断该疾病，对风险分层和遗传咨询具有重要意义。 (C) 2011 年葡萄牙心脏病协会。由 Elsevier Espana, S.L. 出版版权所有。
Background: Sarcomeric hypertrophic cardiomyopathy has heterogeneous phenotypic expressions, of which sudden cardiac death is the most feared. A genetic diagnosis is essential to identify subjects at risk in each family. The spectrum of disease-causing mutations in the Portuguese population is unknown.Methods: Seventy-seven unrelated probands with hypertrophic cardiomyopathy were systematically screened for mutations by PCR and sequencing of five sarcomeric genes: MYBPC3, MYH7, TNNT2, TNNI3 and MYL2. Familial cosegregation analysis was performed in most patients.Results: Thirty-four different mutations were identified in 41 (53%) index patients, 71% with familial hypertrophic cardiomyopathy. The most frequently involved gene was MYBPC3 (66%) with 22 different mutations (8 novel) in 27 patients, followed by MYH7 (22%), TNNT2 (12%) and TNNI3 (2.6%). In three patients (7%), two mutations were found in MYBPC3 and/or MYH7. Additionally, 276 relatives were screened, leading to the identification of a mean of three other affected relatives for each pedigree with the familial form of the disease.Conclusions: Disease-associated mutations were identified mostly in familial hypertrophic cardiomyopathy, corroborating the idea that rarely studied genes may be implicated in sporadic forms. Private mutations are the rule, MYBPC3 being the most commonly involved gene. Mutations in MYBPC3 and MYH7 accounted for most cases of sarcomere-related disease. Multiple mutations in these genes may occur, which highlights the importance of screening both. The detection of novel mutations strongly suggests that all coding regions should be systematically screened. Genotyping in hypertrophic cardiomyopathy enables a more precise diagnosis of the disease, with implications for risk stratification and genetic counseling. (C) 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier Espana, S.L. All rights reserved.