A GENE FOR AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR-DYSTROPHY IN MANITOBA HUTTERITES MAPS TO CHROMOSOME REGION 9Q31-Q33 - EVIDENCE FOR ANOTHER LIMB-GIRDLE MUSCULAR-DYSTROPHY LOCUS

Characterized by proximal muscle weakness and wasting, limb-girdle mus cular dystrophies (LGMDs) are a heterogeneous group of clinical disord ers. Previous reports have documented either autosomal dominant or aut osomal recessive modes of inheritance, with genetic linkage studies pr oviding evidence for the existence of at least 12 distinct loci. Gene products have been identified for five genes responsible for autosomal recessive forms of the disorder. We performed a genome scan using poo led DNA from a large Hutterite kindred in which the affected members d isplay a mild form of autosomal recessive LGMD. A total of 200 markers were used to screen pools of DNA from patients and their siblings. Li nkage between the LGMD locus and D9S302 (maximum LOD score 5.99 at rec ombination fraction .03) was established. Since this marker resides wi thin the chromosomal region known to harbor the gene causing Fukuyama congenital muscular dystrophy (FCMD), we expanded our investigations, to include additional markers in chromosome region 9q31-q34.1. Haploty pe analysis revealed five recombinations that place the LGMD locus dis tal to the FCMD locus. The LGMD locus maps close to D9S934 (maximum mu ltipoint LOD score 7.61) in a region that is estimated to be similar t o 4.4 Mb (Genetic Location Database composite map). On the basis of an inferred ancestral recombination, the gene may lie in a 300-kb region between D9S302 and D9S934. Our results provide compelling evidence th at yet another gene is involved in LGMD; we suggest that it be named ' 'LGMD2H.''.