title: High incidence of 550delA mutation of CAPN3 in LGMD2 patients from Russia.
abstract: Autosomal recessive limb gird muscular dystrophy (LGMD2) is a clinically and genetically heterogeneous group of diseases that are characterized by progressive atrophy and weakness of the proximal limb muscles. At least eight genetic loci leading to LGMD2 are recognized. The proportion of particular gene involved in producing different forms of LGMD2 shows a marked geographical variation. We studied 19 LGMD2 patients from Russia (15 families) and found calpain 3 (CAPN3) gene mutations in most of the patients studied. Sequence analysis of the fourth exons revealed two sibs - heterozygous compound for a 15-bp deletion (nt598-612) and 550 adenine deletion, and two sibs homozygous for a 550delA. We developed assay based on allele specific amplification (ASA) for rapid screening of the 550delA. The ASA assay of the LGMD2 patients under study showed that 7 patients from 6 families were homozygous for 550delA and 7 patients from 4 families were heterozygous for 550delA. A linkage analysis employing four microsatellites flanking the LGMD2A locus was performed. We found complete haplotype identity in most cases what favors the possibility of a common founder. Heterozygous carriers of 550delA were found in general population. The crude estimate of the mutation frequency is 1/150. Hum Mutat 15:295, 2000.
authors.affiliation: Institute of Molecular Genetics, RAS, Moscow. tpogoda@img.ras.ru
authors.forename: T V
authors.initials: TV
authors.lastname: Pogoda
authors.forename: I N
authors.initials: IN
authors.lastname: Krakhmaleva
authors.forename: N A
authors.initials: NA
authors.lastname: Lipatova
authors.forename: N I
authors.initials: NI
authors.lastname: Shakhovskaya
authors.forename: S S
authors.initials: SS
authors.lastname: Shishkin
authors.forename: S A
authors.initials: SA
authors.lastname: Limborska
mesh_terms: D002154:Calpain / Q000235:genetics*; D006239:Haplotypes; D007527:Isoenzymes; D009124:Muscle Proteins; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012426:Russia
chemical_list: D007527:Isoenzymes; D009124:Muscle Proteins; D010446:Peptide Fragments; C105884:CAPN3 protein, human; D002154:Calpain