Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy.
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.
Minetti
C
C
Servizio Malattie Neuro-Muscolari, Universitá di Genova, Istituto Giannina Gaslini, Genoa, Italy. minettic@unige.it
Sotgia
F
F
Bruno
C
C
Scartezzini
P
P
Broda
P
P
Bado
M
M
Masetti
E
E
Mazzocco
M
M
Egeo
A
A
Donati
M A
MA
Volonte
D
D
Galbiati
F
F
Cordone
G
G
Bricarelli
F D
FD
Lisanti
M P
MP
Zara
F
F
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
D051244:Caveolin 3; D022461:Caveolins; D018076:DNA, Complementary; D008565:Membrane Proteins