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-myosin heavy
chain and in the cardiac myosin binding protein C genes in a family
with hypertrophic cardiomyopathy
a Service de Biochimie
B, Groupe Hospitalier Pitié-Salpêtrière, 47 Bld de l'Hôpital,
75651 Paris Cedex 13, France, b Service de Cardiologie, Groupe
Hospitalier Pitié-Salpêtrière, 47 Bld de l'Hôpital, 75651 Paris Cedex 13, France, c INSERM U523, Institut de Myologie,
Groupe Hospitalier Pitié-Salpêtrière, 47 Bld de l'Hôpital,
75651 Paris Cedex 13, France, d Service
de Cardiologie, Hôpital Ambroise Paré, Boulogne, France, e Centre Hospitalier de Fort de France,
Martinique, f URA CNRS 1922, Généthon, Evry, France, g Service de Cardiologie, Hôpital Boucicaut,
Paris, France
Correspondence to: Dr Hainque.
Received 11
August 1998;
Revised version accepted for publication 1 March 1999
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 
-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.
-myosin
heavy chain gene;
cardiac myosin binding protein C gene
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