Journal of Molecular Medicine

, Volume 76, Issue 3–4, pp 208–214

Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy

  • Jeanne Flavigny
  • Pascale Richard
  • Richard Isnard
  • Lucie Carrier
  • Philippe Charron
  • Gisèle Bonne
  • Jean-François Forissier
  • Michel Desnos
  • Olivier Dubourg
  • Michel Komajda
  • Ketty Schwartz
  • B. Hainque
ORIGINAL ARTICLE

DOI: 10.1007/s001090050210

Cite this article as:
Flavigny, J., Richard, P., Isnard, R. et al. J Mol Med (1998) 76: 208. doi:10.1007/s001090050210

Abstract

 Five disease genes encoding sarcomeric proteins and associated with familial and classical forms of hypertrophic cardiomyopathy have been determined since 1989. In 1996 two other genes encoding ventricular regulatory and essential myosin light chains were shown to be associated with a particular phenotype of the disease characterized by mid left ventricular obstruction. The aim of the present study was to search for mutations in the ventricular regulatory myosin light chain gene (MYL2), located on chromosome 12q23q24.3, in a panel of 42 probands presenting a classical phenotype of familial hypertrophic cardiomyopathy. Single-strand conformation polymorphism analysis was used to search for mutations in the coding segments of the MYL2 gene, and the abnormal products were sequenced. Two novel missense mutations, Phe18Leu in exon 2 and Arg58Gln in exon 4 were identified in three unrelated families. None of the affected patients had hypertrophy localized only at the level of the papillary muscle with mid left ventricular obstruction. By analysis of genetic recombinations, one of these mutations identified in a large family allowed us to refine the localization of the MYL2 gene on the genetic map, in an interval of 6 cM containing six informative microsatellite markers. In conclusion, we show that mutations in the MYL2 gene may be involved in familial and classical forms of hypertrophic cardiomyopathy, and we provide new tools for the genetic analysis of patients with familial hypertrophic cardiomyopathy.

Key words Cardiomyopathy Hypertrophied ventricle Regulatory myosin light chain Chromosome 12 Haplotype analysis Genetic localization 

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Jeanne Flavigny
    • 1
  • Pascale Richard
    • 1
  • Richard Isnard
    • 2
  • Lucie Carrier
    • 3
  • Philippe Charron
    • 2
  • Gisèle Bonne
    • 3
  • Jean-François Forissier
    • 4
  • Michel Desnos
    • 4
  • Olivier Dubourg
    • 4
  • Michel Komajda
    • 2
  • Ketty Schwartz
    • 3
  • B. Hainque
    • 1
  1. 1.Biochimie B, and IFR de Physiopathologie et de Génétique Cardiovasculaire, Hôpital Pitié-Salpêtrière, 47 Bd. de l’Hôpital, F-75013 Paris, FranceFR
  2. 2.Groupe des Myocardiopathies de la Société Française de Cardiologie, and IFR de Physiopathologie et de Génétique Cardiovasculaire, Hôpital Pitié-Salpêtrière, 47 Bd. de l’Hôpital, F-75013 Paris, FranceFR
  3. 3.INSERM UR153, and IFR de Physiopathologie et de Génétique Cardiovasculaire, Hôpital Pitié-Salpêtrière, 47 Bd de l’Hôpital, F-75013 Paris, FranceFR
  4. 4.Groupe des Myocardiopathies de la Société Française de Cardiologie, Hôpital Pitié-Salpêtrière, 47 Bd de l’Hôpital, F-75013 Paris, FranceFR

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