title: A founder mutation in the gamma-sarcoglycan gene of gypsies possibly predating their migration out of India.
abstract: We investigated the molecular basis of a severe form of early onset autosomal recessive muscular dystrophy with sarcoglycan (SG) deficiency in seven large Gypsy families living in different parts of Western Europe and apparently not closely related. They were linked to the LGMD2C locus (13q12) suggesting a primary defect in the gamma-SG gene coding for the 35 kDa dystrophin-associated glycoprotein. All of the 18 investigated patients were homozygous for the same G-->A transition in codon 283 producing the replacement of a conserved cysteine of the extra-cellular domain of the protein by a tyrosine. All affected chromosomes in homozygous and heterozygous relatives carried the same allele 5 of the intragenic marker D13S232. Flanking markers were studied to delineate a common ancestral haplotype, the size of which was used to compute the date of the founding mutation. We found evidence that the mutation occurred between 60 and 200 generations ago, therefore possibly predating the commonly accepted date of migration of the Gypsy ancestors out of India.
authors.affiliation: INSERM 129, Hôpital Cochin, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Piccolo
authors.forename: M
authors.initials: M
authors.lastname: Jeanpierre
authors.forename: F
authors.initials: F
authors.lastname: Leturcq
authors.forename: C
authors.initials: C
authors.lastname: Dodé
authors.forename: K
authors.initials: K
authors.lastname: Azibi
authors.forename: A
authors.initials: A
authors.lastname: Toutain
authors.forename: L
authors.initials: L
authors.lastname: Merlini
authors.forename: L
authors.initials: L
authors.lastname: Jarre
authors.forename: C
authors.initials: C
authors.lastname: Navarro
authors.forename: R
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: F M
authors.initials: FM
authors.lastname: Tomé
authors.forename: J A
authors.initials: JA
authors.lastname: Urtizberea
authors.forename: J S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: K P
authors.initials: KP
authors.lastname: Campbell
authors.forename: J C
authors.initials: JC
authors.lastname: Kaplan
mesh_terms: D015415:Biomarkers; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005828:Genetics, Population; D006801:Humans; D007194:India / Q000208:ethnology; D008562:Membrane Glycoproteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000208:ethnology* / Q000235:genetics; D006178:Romani People; D049031:Sarcoglycans
chemical_list: D015415:Biomarkers; D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D049031:Sarcoglycans