A new familial amyotrophic lateral sclerosis locus on chromosome 16q12.1-16q12.2

Abstract

Familial amyotrophic lateral sclerosis (FALS) affects 5%-10% of cases of amyotrophic lateral sclerosis (ALS) and is inherited as an autosomal dominant condition with incomplete penetrance. One-fifth of these cases of FALS are associated with mutations in copper/zinc-dependent superoxide dismutase (SOD1), but the gene defect in the remaining 80% of familial cases is, as yet, unknown. We have carried out a preliminary genome screen, using a U.K. resource of families lacking SOD1 mutations, to identify other potential disease loci and have identified a putative locus on chromosome 16q12.1-q12.2. The region associated with disease was further refined in the major family that contributed to this result and was localized to D16S409-D16S3032, a 14.74-cM genetic interval that corresponds to a physical distance of 6,6 Mb, which coincides with a region independently identified by two further research groups in the United States and the United Kingdom.