RT Journal Article
SR Electronic
T1 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
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 542
OP 545
DO 10.1136/jmg.36.7.542
VO 36
IS 7
A1 Pascale Richard
A1 Richard Isnard
A1 Lucie Carrier
A1 Olivier Dubourg
A1 Yves Donatien
A1 Bénédicte Mathieu
A1 Gisèle Bonne
A1 Françoise Gary
A1 Philippe Charron
A1 Albert Hagege
A1 Michel Komajda
A1 Ketty Schwartz
A1 Bernard Hainque
YR 1999
UL http://jmg.bmj.com/content/36/7/542.abstract
AB 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.