title: Two novel CAV3 gene mutations in Japanese families.
abstract: Caveolin-3 deficiency is a rare, autosomal dominant, muscle disorder caused by caveolin-3 gene (CAV3) mutations and consists of four clinical phenotypes: limb-girdle muscular dystrophy type 1C (LGMD-1C), rippling muscle disease, distal myopathy, and familial hyperCKemia. So far, only 13 mutations have been reported. We here report two novel heterozygous mutations, 96C>G (N32K) and 128T>A (V43E), in the CAV3 gene in two unrelated Japanese families with LGMD-1C. Both probands presented with elevated serum CK level with calf muscle hypertrophy in their childhood but without apparent muscle weakness. However, their mothers showed mild limb-girdle weakness in addition to high CK level. Caveolin-3 was deficient and caveolae were lacking in muscles from both patients. Our data confirm that caveolin-3 deficiency causes LGMD-1C and expand the variability in CAV3 gene mutations.
authors.affiliation: Department of Neuromuscular Research, National Center of Neurology and Psychiatry (NCNP), National Institute of Neuroscience, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Sugie
authors.forename: Kumiko
authors.initials: K
authors.lastname: Murayama
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Murakami
authors.forename: Mika
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: D000328:Adult; D051244:Caveolin 3; D022461:Caveolins / Q000172:deficiency* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000378:metabolism; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D016189:Dystrophin / Q000378:metabolism; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D006984:Hypertrophy / Q000235:genetics / Q000473:pathology; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051244:Caveolin 3; D022461:Caveolins; C114839:DYSF protein, human; D000073939:Dysferlin; D016189:Dystrophin; D008565:Membrane Proteins; D009124:Muscle Proteins; D003402:Creatine Kinase