限制型心肌病中的MYH7突变

MYH7 Mutations in Restrictive Cardiomyopathy.

作者信息

Zhao Yiqi, Liu Shun, Mo Han, Hua Xiumeng, Chen Xiao, Zhang Yue, Wang Weiteng, Zhao Qian, Song Jiangping

机构信息

Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

JACC Adv. 2025 May;4(5):101693. doi: 10.1016/j.jacadv.2025.101693. Epub 2025 Apr 25.

DOI:10.1016/j.jacadv.2025.101693

PMID:40286359

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12102527/

Abstract

BACKGROUND

Restrictive cardiomyopathy (RCM) is a rare cardiac disease characterized by impaired ventricular filling and relaxation, with preserved systolic function. This study investigates the genetic basis of RCM and its impact on clinical outcomes, particularly heart transplantation (HTx).

OBJECTIVES

The aim of the study was to identify genetic variations associated with RCM and assess their impact on disease progression and HTx necessity.

METHODS

A retrospective analysis was conducted on 94 RCM patients from Fuwai Hospital (2003-2021), diagnosed via echocardiography or pathological examination. Whole exome sequencing screened patient samples for variants in key genes associated with RCM, validated via Sanger sequencing. Histopathological analysis of explanted hearts included systematic sampling from ventricles and interventricular septum, with Masson's trichrome staining for fibrosis quantification.

RESULTS

Genetic variants were identified in 54% of patients, with a higher prevalence in HTx patients (73%) compared to non-HTx patients (27%). Myosin heavy chain 7 (MYH7) mutations were found in 15% of cases, significantly associated with HTx (P < 0.001) and atrial fibrillation (P = 0.025). Patients with MYH7 mutations exhibited extensive fibrosis in the interventricular septum compared to nonmutation patients (P < 0.05). The mean age at diagnosis was 47.8 years, with HTx patients diagnosed at a younger age (mean 36.0 years) and transplanted at a mean age of 37.4 years, compared to non-HTx patients diagnosed at a mean age of 57.9 years. The median follow-up time was 5 years.

CONCLUSIONS

Genetic variations, particularly in the MYH7 gene, are significant risk factors for RCM progression and HTx. Genetic screening may guide early interventions, while fibrosis and MYH7 pathways offer potential therapeutic targets.

摘要

背景

限制型心肌病（RCM）是一种罕见的心脏疾病，其特征为心室充盈和舒张功能受损，而收缩功能保留。本研究调查RCM的遗传基础及其对临床结局的影响，尤其是对心脏移植（HTx）的影响。

目的

本研究的目的是识别与RCM相关的基因变异，并评估其对疾病进展和HTx必要性的影响。

方法

对阜外医院94例RCM患者（2003 - 2021年）进行回顾性分析，这些患者通过超声心动图或病理检查确诊。全外显子测序筛查患者样本中与RCM相关的关键基因变异，通过桑格测序进行验证。对移植心脏的组织病理学分析包括从心室和室间隔进行系统取样，用Masson三色染色法进行纤维化定量分析。

结果

54%的患者检测到基因变异，与非HTx患者（27%）相比，HTx患者中基因变异的患病率更高（73%）。15%的病例中发现肌球蛋白重链7（MYH7）突变，与HTx（P < 0.001）和心房颤动（P = 0.025）显著相关。与无MYH7突变的患者相比，有MYH7突变的患者室间隔出现广泛纤维化（P < 0.05）。诊断时的平均年龄为47.8岁，HTx患者诊断时年龄较轻（平均36.0岁），平均37.4岁时接受移植，而非HTx患者诊断时的平均年龄为57.9岁。中位随访时间为5年。