title: Enrichment of the R77C alpha-sarcoglycan gene mutation in Finnish LGMD2D patients.
abstract: Limb-girdle muscular dystrophy 2D (LGMD2D) is caused by mutations in the alpha-sarcoglycan gene (SGCA). The most frequently reported mutation, 229CGC>TGC (R77C) in exon 3 of SGCA, results in the substitution of arginine by cysteine. We present here the clinical, immunohistochemical, and genetic data of 11 Finnish patients with LGMD2D caused by mutations in SGCA. Mutational analysis showed 10 patients homozygous and 1 compound heterozygous for R77C. A wide spectrum of SGCA mutations has been reported previously. Our results show an enrichment of R77C in Finland, further underlined by the observed carrier frequency of 1 per 150. According to the annual birth rate of approximately 60,000 in Finland, one LGMD2D patient with a homozygous mutation is expected to be born every 1 or 2 years on average. The presence of an ancient founder mutation is indicated by the fact that all patients shared a short common haplotype extending > or = 790 kilobases. Our results emphasize the need to include the SGCA gene R77C mutation test in routine DNA analyses of severe dystrophinopathy-like muscular dystrophies in Finland, and suggest that the applicability of this test in other populations should be studied as well.
authors.affiliation: Folkhälsan Institute of Genetics and Department of Medical Genetics, University of Helsinki, Biomedicum, Helsinki, Finland. peter.hackman@helsinki.fi
authors.forename: P
authors.initials: P
authors.lastname: Hackman
authors.forename: V
authors.initials: V
authors.lastname: Juvonen
authors.forename: J
authors.initials: J
authors.lastname: Sarparanta
authors.forename: M
authors.initials: M
authors.lastname: Penttinen
authors.forename: T
authors.initials: T
authors.lastname: Aärimaa
authors.forename: M
authors.initials: M
authors.lastname: Uusitalo
authors.forename: M
authors.initials: M
authors.lastname: Auranen
authors.forename: H
authors.initials: H
authors.lastname: Pihko
authors.forename: R
authors.initials: R
authors.lastname: Alén
authors.forename: M
authors.initials: M
authors.lastname: Junes
authors.forename: T
authors.initials: T
authors.lastname: Lönnqvist
authors.forename: H
authors.initials: H
authors.lastname: Kalimo
authors.forename: B
authors.initials: B
authors.lastname: Udd
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D016001:Confidence Intervals; D005260:Female; D005387:Finland; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation; D049031:Sarcoglycans / Q000235:genetics*
chemical_list: D049031:Sarcoglycans