© 1995 Oxford University Press
OTHER |
Genetic heterogeneity of autosomal recessive limbgirdle muscular dystrophy in a genetic isolate (Amish) and evidence for a new locus
1Généthon 1 rue de I'Internationale, BP60, 91002 Evry, USA 2Fondation Jean Dausset/CEPH 27 rue Juliette Dodu, 75010 Paris, France 3Indiana University School of Medicine 975 West Walnut Street, Indianapolis, IN 46202-5251, USA 4Institut National de la Santé et de la Recherche Médicale, U153, and Centre National de la Recherche Scientifique 17 rue du Fer à Moulin, 75005 Paris, France 5Division of Clinical and Molecular Genetics, Henry Ford Hospital Detroit, MI 48202, USA
*To whom correspondence should be addressed
Received November 7, 1994; Revised December 6, 1994; Accepted December 6, 1994
Limb-girdle muscular dystrophy (LGMD) is a hereditary myopathy presenting clinical and genetic hetero geneity. 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 hetero geneity of LGMD in an Indiana Amish isolate. Further more, 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.