title: Genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy in a genetic isolate (Amish) and evidence for a new locus.
abstract: Limb-girdle muscular dystrophy (LGMD) is a hereditary myopathy presenting clinical and genetic heterogeneity. In 1991, a recessive form (LGMD2A) was linked to chromosome 15q in a genetic isolate from the Isle of La Réunion. Confirmation of this localization was subsequently reported in Brazilian and northern Indiana Amish pedigrees. Here we report the exclusion of the LGMD2A locus in six Amish kindreds from southern Indiana that are related by multiple consanguineous links to the same northern Indiana families in which the involvement of the chromosome 15 locus was previously demonstrated. These findings indicate unexpected genetic heterogeneity of LGMD in an Indiana Amish isolate. Furthermore, genetic analyses also ruled out the possible involvement of the chromosome 2 locus recently described (LGMD2B), thus demonstrating that a mutation within at least one additional locus leads to this condition. Several candidate genes putatively involved in neuromuscular disorders were also excluded.
authors.affiliation: Généthon, Evry, France.
authors.forename: V
authors.initials: V
authors.lastname: Allamand
authors.forename: O
authors.initials: O
authors.lastname: Broux
authors.forename: N
authors.initials: N
authors.lastname: Bourg
authors.forename: I
authors.initials: I
authors.lastname: Richard
authors.forename: J A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: M E
authors.initials: ME
authors.lastname: Hodes
authors.forename: P M
authors.initials: PM
authors.lastname: Conneally
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: C E
authors.initials: CE
authors.lastname: Jackson
authors.forename: J S
authors.initials: JS
authors.lastname: Beckmann
mesh_terms: D002884:Chromosomes, Human, Pair 15; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007196:Indiana; D009136:Muscular Dystrophies / Q000235:genetics*; D010375:Pedigree; D044465:White People
chemical_list: D005819:Genetic Markers