A missense mutation in the beta myosin heavy chain gene is a predictor of premature sudden death in patients with hypertrophic cardiomyopathy

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Bibliographic Details
Title translated into German:Eine stille Mutation in der schweren Kette des beta-Myosins ist Vorlaeufer des vorzeitigen ploetzlichen Todes von Patienten mit hypertropher Kardiomyopathie
Author:Marian, Ali Jalilian; Kelly, Daniel; Mares, Adolph; Fitzgibbons, Jill; Caira, Teresa; Qun-Tao; Hill, Rita; Perryman, Benjamin M.; Roberts, Robert
Published in:The Journal of sports medicine and physical fitness
Published:34 (1994), 1 , S.1-10, Lit.
Format: Publications (Database SPOLIT)
Publication Type: Journal article
Media type: Print resource
ISSN:0022-4707, 1827-1928
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Identification number:PU199506101495

Author's abstract

Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant disease with protean clinical manifestations, ranging from asymptomatic to that of severe heart failure or sudden death. There ist no known parameter in individuals with hypertrophic cardiomyopathy (HCM) that predicts a specific clinical event. This is particularly troublesome for premature sudden death that frequently occurs in young athletes without prior symptoms. Recent identifications of mutations in the beta-myosin heavy chain (betaMHC) gene that co-segregate with the inheritance of the disease provides an opportunity to determine whether certain mutations are more likely to induce a particular clinical event. In this study we analyzed the genotype and phenotype of individuals from two unrelated families with HCM in which the affected individuals have the same missense mutation in exon 13 (G1208A) of the coding sequence for betaMHC. Results: We studied 54 individuals from the two families, 21 were affected with HCM of which eleven died prematurely, eight from sudden cardiac death. While most of the nine affected individuals studied had septal hypertrophy, three had concentric hypertrophy and six, left ventricular outflow tract obstruction. Onset of symptoms was in the second decade of life. Electrophoretic separation of the digested DNA (exon 13) from unaffected individuals provided two fragments of 84 and 70 bp in size, as expected. In contrast, DNA from individuals affected with HCM showed four fragments of 84 bp, 70 bp, 52 bp and 32 bp indicating they inherited the mutation. In only one 10 year old male was the mutation present without evidence of HCM which gives an overall penetrance of 86%. Conclusions: The missense mutation in exon 13 of the betaMHC gene in individuals with FHCM is associated with high penetrance, highly variable expressivity, severe disease, early in onset and a high incidence of premature sudden death. Based on these results we recommend individuals from families with HCM be screened for this missense mutation and if positive, be counselled to avoid combative sports, as it is these activities that often precipitate sudden death. Verf.-Referat