Mutations in TRIM63 cause an autosomal-recessive form of hypertrophic cardiomyopathy

Author:

Salazar-Mendiguchía JoelORCID,Ochoa Juan Pablo,Palomino-Doza Julian,Domínguez Fernando,Díez-López Carles,Akhtar Mohammed,Ramiro-León Soraya,Clemente María M,Pérez-Cejas Antonia,Robledo María,Gómez-Díaz Iria,Peña-Peña María Luisa,Climent Vicente,Salmerón-Martínez Francisco,Hernández Celestino,García-Granja Pablo EORCID,Mogollón M Victoria,Cárdenas-Reyes Ivonne,Cicerchia Marcos,García-Giustiniani Diego,Lamounier Jr. Arsonval,Gil-Fournier Belén,Díaz-Flores Felícitas,Salguero Rafael,Santomé Luis,Syrris Petros,Olivé Montse,García-Pavía Pablo,Ortiz-Genga Martín,Elliott Perry M.ORCID,Monserrat Lorenzo,

Abstract

ObjectiveUp to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM.MethodsTRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls.ResultsSixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15–69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%).ConclusionTRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction.

Funder

European Reference Network on Rare and Complex Diseases of the Heart

Publisher

BMJ

Subject

Cardiology and Cardiovascular Medicine

Cited by 31 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3