Private β- and γ-sarcoglycan gene mutations: Evidence of a founder effect in Northern Italy

Autosomal recessive muscular dystrophies called 'sarcoglycanopathies' result from mutations in the genes encoding α-, β-, γ-, or δ-sarcoglycan complex components. The present study involved six unrelated families from Northern Italy showing mutations in the β- or γ-sarcoglycan genes. An 8 bp duplication in the β-sarcoglycan gene and 1 bp insertion in the γ- sarcoglycan gene occur with high frequency in our population. These mutations have never been reported thus far in other countries. Many patients are homozygotes for a single mutation, although they derived from non- consanguineous marriages. We suggest that these alleles are 'private' mutations of this geographical region. A panel of highly informative microsatellite markers that map in the β- and γ-sarcoglycan gene locus was used to assess the haplotypes among affected patients and control population, in order to test the presence of linkage disequilibrium. We found that the 8 bp duplication in the β-sarcoglycan gene and the 1 bp insertion in the γ- sarcoglycan gene are in linkage disequilibrium with neighbouring polymorphisms. The recurrence of specific sarcoglycan mutations in Northern Italy is probably due to a founder effect, combined with a relative genetic isolation. (C) 2000 Wiley-Liss, Inc.