engleski

Calpainopathy (LGMD2A) in Croatia: molecular and haplotype analysis

Calpainopathy or limb-girdle muscular dystrophy type 2A (LGMD2A) is one autosomal recessive muscular disorder caused by mutations in calpain3 (CAPN3) gene. We report results concerning LGMD2A obtained during 6-year long prospective and on going genetic and epidemiological study of muscular dystrophies in Croatia. Mutation analysis of 29 unrelated LGMD2A families revealed the presence of 6 different CAPN3 mutations (550delA, R541W, Y537X, delFWSAL, R49H, P82L), accounting for 94.8% of CAPN3 chromosomes on studied population. 550delA was the most frequent mutation, found on 43/58 (74%) analyzed CAPN3 chromosomes, while other five mutations ranged from 2 to 9%. Haplotype analysis done on 38 chromosomes carrying 550delA mutation by 5 highly polymorphic markers flanking CAPN3 gene locus showed the presence of the same haplotype on 66% of analyzed chromosomes. Presented data, together with our previously published results, explain the frequency and the distribution of the 550delA mutation in our country by founder effect and genetic drift. Results of haplotype study are in accordance with some previously reported studies and in favor of hypothesis 550delA being an old, rather than a recurrent mutation. Here reported findings are important for effective diagnostic screening of CAPN3 gene in Croatia and neighboring countries, as well as for accurate genetic counseling.

Calpainopathy; CAPN3 gene mutations; Croatia; epidemiology; genetics; haplotype; LGMD2A; limb-girdle muscular dystrophy type 2A; linkage analysis

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