A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q

Amyotrophic lateral sclerosis (ALS) is an adult-onset degenerative disorder characterized by the death of motor neurons in the cortex, brain stem, and spinal cord. Despite intensive research the basic pathophysiology of ALS r emains unclear. Although most cases are sporadic, similar to 10% of ALS cas es are familial (FALS). Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause similar to 20% of FALS. The gene(s) responsible for the remainin g 80% of FALS remain to be found. Using a large European kindred without SO D1 mutation and with classic autosomal dominant adult-onset ALS, we have id entified a novel locus by performing a genome scan and linkage analysis. Th e maximum LOD score is 4.5 at recombination fraction 0.0, for polymorphism D18S39. Haplotype analysis has identified a 7.5-cM, 8-Mb region of chromoso me 18q21, flanked by markers D18S846 and D18S1109, as a novel FALS locus.