title: Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy.
abstract: Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogeneous group of myopathies, including autosomal dominant and recessive forms. To date, two autosomal dominant forms have been recognized: LGMD1A, linked to chromosome 5q, and LGMD1B, associated with cardiac defects and linked to chromosome 1q11-21. Here we describe eight patients from two different families with a new form of autosomal dominant LGMD, which we propose to call LGMD1C, associated with a severe deficiency of caveolin-3 in muscle fibres. Caveolin-3 (or M-caveolin) is the muscle-specific form of the caveolin protein family, which also includes caveolin-1 and -2. Caveolins are the principal protein components of caveolae (50-100 nm invaginations found in most cell types) which represent appendages or sub-compartments of plasma membranes. We localized the human caveolin-3 gene (CAV3) to chromosome 3p25 and identified two mutations in the gene: a missense mutation in the membrane-spanning region and a micro-deletion in the scaffolding domain. These mutations may interfere with caveolin-3 oligomerization and disrupt caveolae formation at the muscle cell plasma membrane.
authors.affiliation: Servizio Malattie Neuro-Muscolari, Universitá di Genova, Istituto Giannina Gaslini, Genoa, Italy. minettic@unige.it
authors.forename: C
authors.initials: C
authors.lastname: Minetti
authors.forename: F
authors.initials: F
authors.lastname: Sotgia
authors.forename: C
authors.initials: C
authors.lastname: Bruno
authors.forename: P
authors.initials: P
authors.lastname: Scartezzini
authors.forename: P
authors.initials: P
authors.lastname: Broda
authors.forename: M
authors.initials: M
authors.lastname: Bado
authors.forename: E
authors.initials: E
authors.lastname: Masetti
authors.forename: M
authors.initials: M
authors.lastname: Mazzocco
authors.forename: A
authors.initials: A
authors.lastname: Egeo
authors.forename: M A
authors.initials: MA
authors.lastname: Donati
authors.forename: D
authors.initials: D
authors.lastname: Volonte
authors.forename: F
authors.initials: F
authors.lastname: Galbiati
authors.forename: G
authors.initials: G
authors.lastname: Cordone
authors.forename: F D
authors.initials: FD
authors.lastname: Bricarelli
authors.forename: M P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: F
authors.initials: F
authors.lastname: Zara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D015153:Blotting, Western; D051244:Caveolin 3; D022461:Caveolins; D002648:Child; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D005192:Family Health; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry; D009136:Muscular Dystrophies / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010375:Pedigree; D017386:Sequence Homology, Amino Acid
chemical_list: D051244:Caveolin 3; D022461:Caveolins; D018076:DNA, Complementary; D008565:Membrane Proteins