Department of Cardiology, Motol University Hospital, 2nd Faculty of Medicine, Charles University, V Uvalu 84, 15006 Prague, Czech Republic.
Int J Mol Sci. 2021 Sep 27;22(19):10401. doi: 10.3390/ijms221910401.
Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with an estimated prevalence of up to 1 in 200 individuals. In the majority of cases, HCM is considered a Mendelian disease, with mainly autosomal dominant inheritance. Most pathogenic variants are usually detected in genes for sarcomeric proteins. Nowadays, the genetic basis of HCM is believed to be rather complex. Thousands of mutations in more than 60 genes have been described in association with HCM. Nevertheless, screening large numbers of genes results in the identification of many genetic variants of uncertain significance and makes the interpretation of the results difficult. Patients lacking a pathogenic variant are now believed to have non-Mendelian HCM and probably have a better prognosis than patients with sarcomeric pathogenic mutations. Identifying the genetic basis of HCM creates remarkable opportunities to understand how the disease develops, and by extension, how to disrupt the disease progression in the future. The aim of this review is to discuss the brief history and recent advances in the genetics of HCM and the application of molecular genetic testing into common clinical practice.
肥厚型心肌病（HCM）是一种常见的遗传性心脏病，估计发病率高达每 200 人中就有 1 人。在大多数情况下，HCM 被认为是一种孟德尔疾病，主要为常染色体显性遗传。大多数致病性变异通常在肌节蛋白基因中检测到。如今，HCM 的遗传基础被认为相当复杂。已经描述了与 HCM 相关的 60 多种基因中的数千种突变。然而，对大量基因进行筛查会导致鉴定出许多意义不明的遗传变异，从而使结果的解释变得困难。缺乏致病性变异的患者现在被认为是非孟德尔 HCM，其预后可能比肌节致病性突变患者要好。确定 HCM 的遗传基础为了解疾病的发展提供了极好的机会，并可以扩展到将来如何破坏疾病的进展。本文旨在讨论 HCM 遗传学的简要历史和最新进展，以及分子遗传学检测在常规临床实践中的应用。
