title: Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy.
abstract: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are caused by mutations in 14 and 15 different disease genes, respectively, in a part of the patients and the disease genes for cardiomyopathy overlap in part with that for limb-girdle muscular dystrophy (LGMD). In this study, we examined an LGMD gene encoding caveolin-3 (CAV3) for mutation in the patients with HCM or DCM. A Thr63Ser mutation was identified in a sibling case of HCM. Because the mutation was found at the residue that is involved in the LGMD-causing mutations, we investigate the functional change due to the Thr63Ser mutation as compared with the LGMD mutations by examining the distribution of GFP-tagged CAV3 proteins. It was observed that the Thr63Ser mutation reduced the cell surface expression of caveolin-3, albeit the change was mild as compared with the LGMD mutations. These observations suggest that HCM is a clinical spectrum of CAV3 mutations.
authors.affiliation: Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Hayashi
authors.forename: Takuro
authors.initials: T
authors.lastname: Arimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ueda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shibata
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hohda
authors.forename: Megumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hisae
authors.initials: H
authors.lastname: Hori
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Koga
authors.forename: Naoki
authors.initials: N
authors.lastname: Oka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D051244:Caveolin 3; D022461:Caveolins / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D007438:Introns / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics; D041681:NIH 3T3 Cells; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: C495548:Cav3 protein, mouse; D051244:Caveolin 3; D022461:Caveolins; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins