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J Med Genet 1999;36:542-545 doi:10.1136/jmg.36.7.542
  • Original article

Double heterozygosity for mutations in the β-myosin heavy chain and in the cardiac myosin binding protein C genes in a family with hypertrophic cardiomyopathy

  1. Pascale Richarda,
  2. Richard Isnardb,
  3. Lucie Carrierc,
  4. Olivier Dubourgd,
  5. Yves Donatiene,
  6. Bénédicte Mathieua,
  7. Gisèle Bonnec,
  8. Françoise Garyf,
  9. Philippe Charronb,
  10. Albert Hagegeg,
  11. Michel Komajdab,
  12. Ketty Schwartzc,
  13. Bernard Hainquea
  1. aService de Biochimie B, Groupe Hospitalier Pitié-Salpêtrière, 47 Bld de l’Hôpital, 75651 Paris Cedex 13, France, bService de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, 47 Bld de l’Hôpital, 75651 Paris Cedex 13, France, cINSERM U523, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, 47 Bld de l’Hôpital, 75651 Paris Cedex 13, France, dService de Cardiologie, Hôpital Ambroise Paré, Boulogne, France, eCentre Hospitalier de Fort de France, Martinique, fURA CNRS 1922, Généthon, Evry, France, gService de Cardiologie, Hôpital Boucicaut, Paris, France
  1. Dr Hainque.
  • Received 11 August 1998
  • Revised 1 March 1999

Abstract

Familial hypertrophic cardiomyopathy is a genetically heterogeneous autosomal dominant disease, caused by mutations in several sarcomeric protein genes. So far, seven genes have been shown to be associated with the disease with the β-myosin heavy chain (MYH7) and the cardiac myosin binding protein C (MYBPC3) genes being the most frequently involved.

We performed electrocardiography (ECG) and echocardiography in 15 subjects with hypertrophic cardiomyopathy from a French Caribbean family. Genetic analyses were performed on genomic DNA by haplotype analysis with microsatellite markers at each locus involved and mutation screening by single strand conformation polymorphism analysis. Based on ECG and echocardiography, eight subjects were affected and presented a classical phenotype of hypertrophic cardiomyopathy. Two new mutations cosegregating with the disease were found, one located in the MYH7 gene exon 15 (Glu483Lys) and the other in the MYBPC3 gene exon 30 (Glu1096 termination codon). Four affected subjects carried the MYH7 gene mutation, two the MYBPC3 gene mutation, and two were doubly heterozygous for the two mutations. The doubly heterozygous patients exhibited marked left ventricular hypertrophy, which was significantly greater than in the other affected subjects.

We report for the first time the simultaneous presence of two pathological mutations in two different genes in the context of familial hypertrophic cardiomyopathy. This double heterozygosity is not lethal but is associated with a more severe phenotype.

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