Private beta- and gamma-sarcoglycan gene mutations: evidence of a founder effect in Northern Italy

Hum Mutat. 2000;16(1):13-7. doi: 10.1002/1098-1004(200007)16:1<13::AID-HUMU3>3.0.CO;2-V.

Abstract

Autosomal recessive muscular dystrophies called "sarcoglycanopathies" result from mutations in the genes encoding alpha-, beta-, gamma-, or delta-sarcoglycan complex components. The present study involved six unrelated families from Northern Italy showing mutations in the beta- or gamma-sarcoglycan genes. An 8 bp duplication in the beta-sarcoglycan gene and 1 bp insertion in the gamma-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 beta- and gamma-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 beta-sarcoglycan gene and the 1 bp insertion in the gamma-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cytoskeletal Proteins / genetics*
  • DNA / analysis
  • DNA / blood
  • DNA Primers / chemistry
  • Dystroglycans
  • Dystrophin / genetics*
  • Female
  • Founder Effect*
  • Gene Duplication
  • Gene Frequency
  • Humans
  • Italy / epidemiology
  • Linkage Disequilibrium
  • Male
  • Membrane Glycoproteins / genetics*
  • Microsatellite Repeats / genetics
  • Muscular Dystrophies / blood
  • Muscular Dystrophies / ethnology
  • Muscular Dystrophies / genetics*
  • Mutation*
  • Sarcoglycans

Substances

  • Cytoskeletal Proteins
  • DAG1 protein, human
  • DNA Primers
  • Dystrophin
  • Membrane Glycoproteins
  • Sarcoglycans
  • Dystroglycans
  • DNA