title: Beta-myosin heavy chain gene mutations and hypertrophic cardiomyopathy in Austrian children.
abstract: Hypertrophic cardiomyopathy occurs in two variants, either as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. Different genes coding sarcomeric proteins of the heart have been identified as causing hypertrophic cardiomyopathy. Missense mutations in the cardiac beta-myosin heavy chain gene are found in 30% of all cases of familial hypertrophic cardiomyopathy. We screened the beta-myosin heavy chain gene of children of nine Austrian families with hypertrophic cardiomyopathy (referred to as group A) and of seven children with sporadic hypertrophic cardiomyopathy (referred to as group B). We were able to find two previously described (V606M, R453C) and two unknown missense mutations (V406M, R663H) in group A. Additionally, in two children of group B we could identify one already known missense mutation, R249Q as well as one previously unknown missense mutation, M877K. The genetically affected children of group A developed no or only mild clinical symptoms, whereas the children of group B with genetically confirmed sporadic hypertrophic cardiomyopathy showed manifest left ventricular hypertrophy and clinical symptoms including chest pain and dyspnoea. Clinical symptoms among the adults of group A, suffering from familial hypertrophic cardiomyopathy, varied significantly. We therefore believe V406M to be a more malignant missense mutation, probably linked with sudden death in the affected family, than R663H, which seems to be more benign causing late-onset hypertrophic cardiomyopathy and mild clinical symptoms in the affected family members.
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, University of Vienna, Währinger Gürtel 18-20, Vienna, A-1090, Austria. Susanne.Greber-Platzer@akh-wien.ac.at
authors.forename: S
authors.initials: S
authors.lastname: Greber-Platzer
authors.forename: M
authors.initials: M
authors.lastname: Marx
authors.forename: C
authors.initials: C
authors.lastname: Fleischmann
authors.forename: C
authors.initials: C
authors.lastname: Suppan
authors.forename: M
authors.initials: M
authors.lastname: Dobner
authors.forename: M
authors.initials: M
authors.lastname: Wimmer
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D001317:Austria / Q000453:epidemiology; D002312:Cardiomyopathy, Hypertrophic / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D004562:Electrocardiography; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation
chemical_list: D018995:Myosin Heavy Chains