C283Y mutation and other C-terminal nucleotide changes in the gamma-sarcoglycan gene in the Bulgarian Gypsy population

Sarcoglycanopathies, affecting the dystrophin-associated sarcoglycan (SG) c omplex, are a heterogeneous group of neuromuscular disorders. A subgroup of these disorders, limb-girdle muscular dystrophy type 2C (LGMD2C) is an aut osomal recessive disorder, clinically manifested as an early onset, severe Duchenne like muscular dystrophy LGMD2C is caused by mutations in the gamma -SG gene, localized on 13q12. Recently a number of mutations have been desc ribed in that gene, among which C283Y, a "private" Gypsy mutation (eight co dons before the 3' end of the gene) is detected. In this article, we report on a single strand conformation polymorphism (SSCP) method for fast C283Y mutation detection, using direct dry blood spot amplification. The method p ermits a large number of samples to be easily screened. To check heterozygo te carriers of C283Y mutation among Gypsy population in Bulgaria, the SSCP analysis was applied on 400 Gypsy newborns from northeast Bulgaria. Our res ults show 2.25% of heterozygosity which means that 1 in 50 Gypsies carries the mutation, Moreover, new SSCP migration patterns were detected that reve aled two polymorphisms still unavailable in the literature. One of these ch anges was 984G-->A, leading to substitution of conserved serine at position 287 with asparagine anal the second one is 1049C-->G at the 3' UTR (untran slated region). The present data could help the understanding the role of t hese sequences for the protein function. Hum Mutat 14:40-44, 1999. (C) 1999 Wiley Liss, Inc.