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
References
Oct 21, 1994·Cell·S ArberP Caroni
Feb 1, 1996·Genes & Development·S Arber, P Caroni
Feb 7, 1997·Cell·S ArberP Caroni
May 1, 2001·Nature Medicine·M PashmforoushK R Chien
Jan 1, 2003·Cell·Ralph KnöllKenneth R Chien
Mar 19, 2003·Circulation·Christian GeierKarl Josef Osterziel
Mar 23, 2005·Molecular Genetics and Metabolism·Bill NewmanKatherine A Siminovitch
Dec 15, 2005·Molecular Genetics and Metabolism·J Martijn BosMichael J Ackerman
May 29, 2008·Human Molecular Genetics·Christian GeierCemil Ozcelik
Nov 28, 2008·Human Mutation·Paal Skytt AndersenHenning Bundgaard
May 5, 2009·Clinical and Translational Science·Ray E HershbergerMichael Litt
Jan 21, 2010·Netherlands Heart Journal : Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation·I A W van RijsingenY M Pinto
Dec 6, 2012·European Heart Journal·Claudio RapezziPerry M Elliott
Sep 1, 2014·European Heart Journal·Perry M ElliottHugh Watkins
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
May 6, 2015·Gene·Elizabeth VafiadakiDespina Sanoudou
Jan 17, 2016·Nucleic Acids Research·Nele HugJavier F Cáceres
Sep 30, 2016·Nature Reviews. Cardiology·Srijita Sen-ChowdhryWilliam J McKenna
Apr 4, 2017·Clinical Genetics·M Sabater-MolinaJ R Gimeno
Apr 25, 2017·Clinical Genetics·A JaninG Millat
Citations
Sep 7, 2019·International Journal of Molecular Sciences·Andreas BrodehlHendrik Milting
Jul 2, 2020·Circulation. Genomic and Precision Medicine·Hélène ChoquetCatherine Schaefer
May 7, 2021·Molecular Diagnosis & Therapy·Alexandre JaninGilles Millat
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