Résumé :
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Recently, recessive mutations in ANO5 gene have been shown to be a major cause of limb-girdle and other types of muscular dystrophy. According to recent studies, LGMD2L is one of the most common LGMDs in Europe, its prevalence being similar to the sarcoglycanopathies. The most common mutation in European populations seems to be c.191dupA (p.N64KfsX15). However, in Finland mutation c.2272C>T (p.R758C) has a frequency of 0,35 % and is probably more common. Our sequencing studies of ANO5 have so far revealed 22 muscular dystrophy patients with various mutations. Fifteen of these patients were of Finnish origin, three patients were American, two Spanish, one Australian and one Italian. The most common mutation in our patient cohort was c.2272C>T that was homozygous in six patients and heterozygous in nine patients. Eleven patients were heterozygous for c.191dupA. In addition we have seen eight other mutations, seven of which are previously unknown. Although most patients had either or both of the common mutations, it is noteworthy that two patients (9 %) were compound heterozygotes for two previously unknown mutations. This suggests that a significant number of patients can not be found by simple screening of one or two mutations. Since we found ten different mutations in 22 patients it is likely that total number of recessive ANO5 mutations is remarkable. Mutations seem to distribute evenly along the gene without a clear mutational hotspot. However, exons 15, 19 and 20 harboured two different mutations each which suggests that these three exons could be especially prone to mutations. It is evident that c.191dupA and c.2272C>T are frequent mutations at least in European populations. Nonetheless, since there are numerous other mutations it is plausible that also some of them occur in high frequencies.
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