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. Results: 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. Conclusions: 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. (C) 2008 Elsevier B.V. All rights reserved.