engleski

Epidemiology and genetics of calpainopathy in Croatia

A 3-year long pilot study concerning aetiology and epidemiology of muscular dystrophy in Croatia had showed that calpainopathy (LGMD2A) was the prevalent autosomal recessive muscular dystrophy in Croatia. Analysis of 50 chromosomes for five CAPN3 mutations (550delA, DFWSAL, R541W, Y357X and R49H) combined with a specific clinical diagnostic strategy has permitted the identification of 90% of CAPN3 mutated alleles. A high prevalence of the 550delA mutation (76% ; 38/50 of CAPN3 chromosomes) became evident. These data led us to screen the general population for the 550delA mutation. 532 random blood samples (presenting 0, 01% of 4, 4 million people of Croatia) were thus collected from healthy blood donors from three different regions of Croatia. We used allele- specific PCR, which proved to be less time-consuming than previously utilised PCR and restriction with Bsa AI. Four healthy 550delA heterozygotes were found making the whole frequency of 1 in 133 (4/532). When analysed by region, the results were quite variable. In 200 donors from the capital city, Zagreb, no carrier was found, neither in a small sample of 68 donors from the northeast region. All 4 carriers originated from a pool of 264 blood donors from islands and mountain region close to the Adriatic Sea. These findings combined with haplotype analysis (using of five microsatellite markers: D15S514, D15S779, D15S782, D15S780, D15S778) confirm that our general population is rather "closed" with probable founder effect in some parts of the country. Observed data are relevant to accurate genetic counselling and patients' testing. Moreover, the high frequency of 550delA mutation found in ten additional neighbouring European countries together with easy detection of 550delA mutation should streamline the genetic analysis having in mind the geographic and ethnic origin of the patients. Last but not least our results combined with published haplotype studies suggest that 550delA, might be specific or one of mutations at least frequent in the East Mediterranean area from which it has probably spread especially across Europe. Accumulation of similar study might give more accurate answer. Practical aspect of our findings are relevant to accurate genetic counselling and patient testing since we lack sensitive and specific biopsy screening methods for detecting patients with calpainopathy. Accordingly, detection of patients relies on the direct detection of gene mutation and our findings should prompt clinicians from our Croatia but also from neighbouring Mediterranean countries to test first this easily and rapidly detectable mutation in patients with presumed calpainopathy.

epidemiology; genetics; calpainopathy; LGMD2A; Croatia

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