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Mol Diagn Ther. 2018 Apr;22(2):219-223. doi: 10.1007/s40291-018-0324-1.

A Novel Missense Mutation p.Gly162Glu of the Gene MYL2 Involved in Hypertrophic Cardiomyopathy: A Pedigree Analysis of a Proband.

Author information

1
Service de Rythmologie, Hôpital Cardiologique Louis-Pradel, 28, avenue du Doyen Jean Lépine, 69677, Bron, France.
2
Université Lyon 1, 69003, Lyon, France.
3
Laboratoire de Cardiogénétique Moléculaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France.
4
Service de Rythmologie, Hôpital Cardiologique Louis-Pradel, 28, avenue du Doyen Jean Lépine, 69677, Bron, France. philippe.chevalier@chu-lyon.fr.
5
Université Lyon 1, 69003, Lyon, France. philippe.chevalier@chu-lyon.fr.

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 next-generation 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 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.

PMID:
29549657
DOI:
10.1007/s40291-018-0324-1
[Indexed for MEDLINE]

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