A Novel Missense Mutation p.Gly162Glu of the Gene MYL2 Involved in Hypertrophic Cardiomyopathy: A Pedigree Analysis of a
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SHORT COMMUNICATION
A Novel Missense Mutation p.Gly162Glu of the Gene MYL2 Involved in Hypertrophic Cardiomyopathy: A Pedigree Analysis of a Proband Pauline Renaudin1,3 • Alexandre Janin2,3 • Gilles Millat2,3
•
Philippe Chevalier1,3
Ó Springer International Publishing AG, part of Springer Nature 2018
Abstract Background Hypertrophic cardiomyopathy (HCM), a common and clinically heterogeneous disease characterized by unexplained ventricular myocardial hypertrophy, is mostly caused by mutations in sarcomeric genes. Identifying the genetic cause is important for management, therapy, and genetic counseling. Methods A molecular diagnosis was performed on a 51-year-old woman diagnosed with HCM using a nextgeneration sequencing workflow based on a panel designed for sequencing the most prevalent cardiomyopathy-causing genes. Segregation analysis was performed on the woman’s family. Results A novel myosin regulatory light chain (MYL2) missense variant, NM_000432.3:c485G[A, p.Gly162Glu, was identified and firstly considered as a putative pathogenic mutation. Among the 27 family members tested, 16 were carriers for the MYL2-p.Gly162Glu mutation, of whom 12 with the phenotype were positive. None of the 11 family members without mutation had cardiomyopathy. Conclusions Genetic analysis combined with a segregation study allowed us to classify this novel MYL2 variation, p.Gly162Glu, as a novel pathogenic mutation leading to a familial form of HCM. Due to absence of fast in vitro
& Philippe Chevalier [email protected] 1
Service de Rythmologie, Hoˆpital Cardiologique LouisPradel, 28, avenue du Doyen Jean Le´pine, 69677 Bron, France
2
Laboratoire de Cardioge´ne´tique Mole´culaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France
3
Universite´ Lyon 1, 69003 Lyon, France
approaches to evaluate the functional impact of missense variants on HCM-causing genes, segregation studies remain, when possible, the easiest approach to evaluate the putative pathogenicity of novel gene variants, more particularly missense ones.
Key Points Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disease for which a segregation study remains, if possible, the easiest strategy to evaluate the pathogenicity of novel variations. Next-generation sequencing (NGS) workflow analysis is an efficient, fast, cheap and highthroughput detection method for pathogenic mutations in HCM-causing genes.
1 Introduction During the past 25 years, major advances in deciphering the genetic bases of human disease have been achieved. However, the integration of these findings into clinical care is challenged by a lack of publicly available and accurate interpretations of the vast amount of human genetic variations identified. For most of them, particularly missense variations, evaluation of their pathogenicity could be improved using segregation studies and/or, if available, functional characterization using in vitro or in vivo systems.
P. Renaudin et al.
Hypertrophic cardiomyopathy (HCM) is the most common type
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