Mutations of calpain 3 gene in patients with sporadic limb-girdle musculardystrophy in Japan

Mutations of the calpain 3 gene, an intracellular calcium-activated neutral protease, is one of the causes of limb-girdle muscular dystrophy (LGMD). W e examined 14 Japanese patients with sporadic LGMD for calpain 3 mutations, and found four mutations in five patients. Three (R461C, D707G and R147P) were novel missense mutations, and one was a splice-site mutation (801 + 1g -->a) resulting in skipping of exons 4 and 5. Of the five patients, three p atients with homozygous missense mutations showed later onset and slower pr ogression than the other two patients with an exon skipping or mRNA loss of unknown cause. It would appear that the occurrence of calpain 3 gene mutat ions in sporadic LGMD in Japan may be quite high since all five patients wi th mutations in this gene were among the 14 patients without apparent famil y history, an incidence of 36%. These findings also suggest that calpain 3 deficiency occurs in both sporadic and familial LGMD and that direct analys is of the calpain 3 gene may be useful in the definitive diagnosis not only of the 15q-linked familial but also of sporadic cases of LGMD. (C) 1999 El sevier Science B.V. All rights reserved.