First identification of homozygous truncating CSRP3 variants in two unrelated cases with hypertrophic cardiomyopathy

Gene
Alexandre JaninG Millat

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with an estimated prevalence of 1/500. More than 40 genes have been reported to cause HCM. Among them, CSRP3 is usually included on HCM gene panels used for molecular diagnosis by next-generation sequencing (NGS). To provide new insights into the pathophysiology of hypertrophic cardiomyopathy, a NGS workflow based on a panel of 48 cardiomyopathies-causing genes was analyzed on a cohort of 542 HCM patients. As expected, this molecular approach led to identify most pathogenic or likely pathogenic variants into prevalent HCM-causing genes: MYBPC3 (123/542; 22.7%), MYH7 (48/542; 8.9%), TNNT2 (12/542; 2.2%), and TNNI3 (10/542; 1.8%). Among MYBPC3 variants, 96 led to a premature stop codon (78%). More surprisingly, our molecular study led also to detect, for the first time, homozygous CSRP3 truncating variants in two unrelated HCM probands. Meta-analysis of rare previously reported CSRP3 variants on HCM probands using ACMG guidelines indicate that only one variation (p.Cys58Gly) could be considered as likely pathogen. By combining meta-analysis results and identification of two unrelated HCM patients with homozygous CSRP3 truncating variants, we sug...Continue Reading

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Citations

Sep 7, 2019·International Journal of Molecular Sciences·Andreas BrodehlHendrik Milting
Jul 2, 2020·Circulation. Genomic and Precision Medicine·Hélène ChoquetCatherine Schaefer
Aug 13, 2021·Frontiers in Physiology·Caroline Michele Marinho MarcianoMônica Corrêa Ledur
Sep 17, 2021·Nature Reviews. Cardiology·Roddy WalshConnie R Bezzina
Sep 25, 2021·The Journal of Gene Medicine·Hao HuangRong Xiang
Nov 20, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Marie-Louise BangJu Chen

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