title: Myosin mutations in hypertrophic cardiomyopathy and functional implications.
abstract: Hypertrophic cardiomyopathy (HCM) can be an inherited disorder. Typically, the inheritance is dominant and genetic cases account for about 50% of all patients with this pathology. Four different HCM loci have been mapped to different chromosomes (no. 1, 11, 14 and 15), yet, only one responsible gene has been identified. It is the beta myosin heavy chain gene on chromosome 14, which is expressed in ventricles and in slow skeletal muscle fibers. A large number of missense mutations has been reported which are predominantly located in the globular head region of the beta myosin. An apparent hot spot of mutation has been detected within exon 13 of the gene, corresponding to amino acid position 403. Although the functional consequences of the various mutations for the activity of beta myosin are not known, by inference and on the basis of published data, it may be suggested that a mutation in position 403 affects the myosin-actin dissociation in the contractile cycle. Despite our knowledge of mutations in the myosin gene, and of many of the pathological sequelas, there still is insufficient information which precludes unequivocal conclusions on the molecular mechanisms by which the pathogenesis of the myosin deficient heart develops. Molecular biology and genetics should help to define the determinants of this disease.
authors.affiliation: Max-Planck-Institut für physiologische und klinische Forschung, Abteilung Experimentielle Kardiologie, Bad Nauheim.
authors.forename: H P
authors.initials: HP
authors.lastname: Vosberg
mesh_terms: D001483:Base Sequence / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000503:physiopathology; D002883:Chromosomes, Human, Pair 14; D004247:DNA / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D018995:Myosin Heavy Chains; D024461:Myosin Type I; D009218:Myosins / Q000235:genetics* / Q000502:physiology
chemical_list: D002148:Calmodulin-Binding Proteins; C062291:MYO1A protein, human; D004247:DNA; D024461:Myosin Type I; D018995:Myosin Heavy Chains; D009218:Myosins