title: Private beta- and gamma-sarcoglycan gene mutations: evidence of a founder effect in Northern Italy.
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.
authors.affiliation: Regional Neuromuscular Center, Department of Neurological and Psychiatric Sciences, University of Padova, Italy. cmusc@ux1.unipd.it
authors.forename: M
authors.initials: M
authors.lastname: Fanin
authors.forename: E P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: C
authors.initials: C
authors.lastname: Angelini
authors.forename: E
authors.initials: E
authors.lastname: Pegoraro
mesh_terms: D000483:Alleles; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000097:blood; D017931:DNA Primers / Q000737:chemistry; D049030:Dystroglycans; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D020440:Gene Duplication; D005787:Gene Frequency; D006801:Humans; D007558:Italy / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D009136:Muscular Dystrophies / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D009154:Mutation; D049031:Sarcoglycans
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D017931:DNA Primers; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans; D004247:DNA