engleski

Mutation and haplotype analysis of calpainopathy (LGMD 2A) in Croatia

INTRODUCTION.Calpainopathy or limb girdle muscular dystrophy type 2A (LGMD 2A ; OMIM 253600) is an autosomal recessive muscular disorder characterized by symmetrical and selective atrophy of proximal limb muscles. It is caused by mutations in CAPN3 gene, coding for calpain 3. We report results concerning LGMD 2A obtained during 6-year long prospective and on going genetic and epidemiological study of muscular dystrophies in Croatia. OBJECTIVES.To determine the CAPN3 mutation spectrum in Croatia, their frequency and geographical distribution, as well as to speculate on origin of some mutations by haplotype analysis. METHODS. CAPN3 mutation analysis included 40 patients from 29 unrelated LGMD 2A families. Individuals selected for haplotype analysis consisted of 35 patients from 25 families and 36 healthy family members (27 of them being heterozygotes for one of CAPN3 mutations). Mutation analysis included allele-specific PCR or combination of PCR and RFLP methods. Haplotype analysis was done by PCR and DNA-PAGE, using 5 highly polymorphic markers (D15S514, D15S779, D15S782, D15S780, D15S778) flanking CAPN3 gene locus. RESULTS. Mutation analysis has revealed the presence of 6 different CAPN3 mutations, accounting for almost 95% of CAPN3 chromosomes in our country. Haplotype analysis done on 38 chromosomes carrying 550delA mutation showed the presence of the same haplotype (2-9-3-4-1) on 66% of analyzed chromosomes.

calpain3; CAPN3; LGMD2A; mutations; haplotypes

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