engleski

Clinical, genetic and epidemiological study of prevalent autosoma recessive limb girdle muscular dystrophies in Croatia

This report concerns results obtained for LGMD2 during prospective 7-years long study on clinical, genetic and epidemiological aspects of muscular dystrophies in Croatia. Clinical and genetic diagnostic strategy adapted to our country of 4, 4 million people was used. Calpainopathy is the prevalent LGMD2. Analysis of 32 apparently unrelated families (50 patients) with CAPN3 gene mutation/s and LGMD has discovered six different CAPN3 mutations: 550delA, R541W, P82L, delFWSAL, R49H, Y537X. In 28 families two CAPN3 alleles were identified. In excluded 4 families with only one known CAPN3 allele, 550delA was present in 3 of 4 alleles, and P82L in one. 550 delA was the most frequent mutation found on 43/56 (77%) analyzed CAPN3 chromosomes ; other five mutations ranged from 11 to 2%. The second, most common LGMD2 seems to be type 2I caused by mutation in FKRP. Six unrelated families with identical C826A mutation were identified. One of 6 homozygous C826A probands was in addition heterozygote for 550delA. Three patients from two unrelated, informative families are affected by presumed MM/LGMD2B. Haplotype analysis using microsatellites flanking the dysferlin gene and non-invasive western blot analysis of DYSF gene from peripheral blood confirmed diagnosis, but mutation(s) is/are still unidentified. Surprisingly, we have identified any sarcoglycanopathy probably because of sampling bias (small number of children) and limited methodology (lack of biopsy and WB of different proteins). Because of high frequency of healthy 550delA heterozygotes (4 in 532 blood donors) and relative frequency of healthy heterozygote for C826A mutation (2 in 807 blood donors) in our general population, we need to know both allele to confirm the diagnosis of LGMD2A and 2I To study natural history of any LGMD2 both alleles must be known as well as genetically homogenous groups should be follow up according to as simple as possible protocol.

limb girgle muscular dystrophy; LGMD2A; calpainopathy; Croatia; clinics; genetics; epidemiology

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