Research Article| Volume 276, ISSUE 1-2, P95-98, January 15, 2009

Phenotypic variability in a Spanish family with a Caveolin-3 mutation


      We report a Spanish family affected from a late onset, hand-involved and autosomal dominant distal myopathy associated to Caveolin-3 mutation. Signs of muscle hyperexcitability and hyperckemia were observed in the youngest relatives but not motor symptoms.

      Patients and methods

      Neurological examination was performed in all members of the family. Muscle biopsy sample was taken from the proband and DNA genomics was amplified for the two exons of Cav-3 by the polymerase chain reaction (PCR) in all the affected members and in three asymptomatic relatives.


      Signs of muscle hyperexcitability and hyperckemia were observed in the affected members from early ages. Cav-3 expression was greatly reduced in the sarcolemma of the proband's muscle. Genetic studies revealed a G → A transition at nucleotide position 80 in exon 1 of the Cav-3 gene (c.80G>A), generating a Arg → Gln change at codon 27 (p.R27Q) of the amino acid chain in heterozygous state, while no mutation was found in unaffected members.


      Signs of muscle hyperexcitability and hyperckemia at early ages may predict the development of a late onset autosomal dominant hand-involved myopathy associated to Cav-3 mutation in the family reported herein.


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        • Song K.S.
        • Scherer P.E.
        • Tang Z.
        • Okamoto T.
        • Li S.
        • Chafel M.
        • et al.
        Expression of Caveolin-3 in skeletal, cardiac and smooth muscle cells.
        J. Biol. Chem. 1996; 271: 15160-15165
        • Ikezu T.
        • Ueda H.
        • Trapp B.D.
        • Nishiyama K.
        • Sha J.F.
        • Volonte D.
        • et al.
        Affinity-purification and characterization of caveolins from the brain: differential expression of caveolin-1,-2 and -3 in brain endothelial and astroglial cell types.
        Brain Res. 1998; 804: 177-192
        • Woodman S.E.
        • Sotgia F.
        • Galbiati F.
        • Minetti C.
        • Lisanti M.P.
        Mutations in caveolin-3 cause four distinct autosomal dominant muscle diseases.
        Neurology. 2004; 62: 538-543
        • Fischer D.
        • Schoroers A.
        • Blümcke I.
        • Urbach H.
        • Zerres K.
        • Mortier W.
        • et al.
        Consequences of a novel caveolin-3 mutation in a large German family.
        Ann. Neurol. 2003; 53: 233-241
        • Yabe I.
        • Kawashima A.
        • Kikuchi S.
        • Higashi T.
        • Fukazawa T.
        • Hamada T.
        • et al.
        Caveolin-3 gene mutation in Japanese with rippling muscle disease.
        Acta Neurol Scand. 2003; 108: 47-51
        • Minetti C.
        • Sotgia F.
        • Bruno C.
        • Scartezzini P.
        • Broda P.
        • Bado M.
        • et al.
        Mutations in the caveolin-3 gene cause autosomal dominant limb girdle muscular dystrophy.
        Nat Genet. 1998; 18: 365-368
        • Tateyama M.
        • Aoki M.
        • Nishino I.
        • Hayashi Y.K.
        • Sekiguchi S.
        • Shiga Y.
        • et al.
        Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy.
        Neurology. 2002; 58: 323-325
        • Torbergsen T.
        Rippling muscle disease.
        Muscle Nerve. 2002; : S103-S107
        • Lamb G.D.
        Rippling muscle disease may be caused by silent action potentials in the tubular system of skeletal muscle fibers.
        Muscle and Nerve. 2005; 31: 652-658