Hong Ying, Fan Zhen, Guo Yi, Ma Hui-Hui, Zeng Sheng-Zhi, Xi Hu-Tao, Yang Jing, Luo Kai, Luo Rong, Li Xiao-Ping
Department of Cardiology, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China.
Department of Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan Province, China.
World J Clin Cases. 2025 May 26;13(15):101272. doi: 10.12998/wjcc.v13.i15.101272.
Hypertrophic cardiomyopathy (HCM) is one of the most prevalent inherited myocardial disorders and is characterized by considerable genetic and phenotypic heterogeneity. A subset of patients with HCM progress to a dilated phase of HCM (DPHCM), which is associated with a poor prognosis; however, the underlying pathogenesis remains inadequately understood.
In this study, we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations. Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy, a heterozygous missense mutation (c.746G>A, p.Arg249Glu) in the gene was identified in the proband (III-5). Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members (II-4, III-4, and IV-3). A total of 26 well-documented patients with DPHCM were identified in the literature. Patients with DPHCM are commonly middle-aged and male. The mean age of patients with DPHCM was 53.43 ± 12.79 years. Heart failure, dyspnoea, and atrial fibrillation were the most prevalent symptoms observed, accompanied by an average left ventricular end-diastolic size of 58.62 mm.
Our findings corroborate the pathogenicity of the (c.746G>A, p.Arg249Glu) mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.
肥厚型心肌病（HCM）是最常见的遗传性心肌疾病之一，其特征是具有显著的遗传和表型异质性。一部分HCM患者会进展为肥厚型心肌病的扩张期（DPHCM），这与预后不良相关；然而，其潜在发病机制仍未得到充分了解。
在本研究中，我们报告了一例涉及家族性DPHCM家系的病例，并对已鉴定出基因突变的DPHCM患者进行了回顾性分析。通过针对与遗传性心肌病相关的312个基因编码区的panel测序，在先证者（III-5）中鉴定出该基因的一个杂合错义突变（c.746G>A，p.Arg249Glu）。随后，Sanger测序在另外三名家庭成员（II-4、III-4和IV-3）中证实了这一致病突变。在文献中总共鉴定出26例有充分记录的DPHCM患者。DPHCM患者通常为中年男性。DPHCM患者的平均年龄为53.43±12.79岁。心力衰竭、呼吸困难和心房颤动是最常见的症状，平均左心室舒张末期内径为58.62mm。
我们的研究结果证实了（c.746G>A，p.Arg249Glu）突变对DPHCM的致病性，并表明Arg249Gln突变可能是高死亡率的原因。
