Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy.
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.
Hayashi
Takeharu
T
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Arimura
Takuro
T
Ueda
Kazuo
K
Shibata
Hiroki
H
Hohda
Shigeru
S
Takahashi
Megumi
M
Hori
Hisae
H
Koga
Yoshinori
Y
Oka
Naoki
N
Imaizumi
Tsutomu
T
Yasunami
Michio
M
Kimura
Akinori
A
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
C495548:Cav3 protein, mouse; D051244:Caveolin 3; D022461:Caveolins; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins