A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2

Amyotrophic lateral sclerosis 2 (ALS2) is an autosomal recessive form of ju venile ALS and has been mapped to human chromosome 2q33. Here we report the identification of two independent deletion mutations linked to ALS2 in the coding exons of the new gene ALS2. These deletion mutations result in fram eshifts that generate premature stop codons. ALS2 is expressed in various t issues and cells, including neurons throughout the brain and spinal cord, a nd encodes a protein containing multiple domains that have homology to RanG EF as well as RhoGEF. Deletion mutations are predicted to cause a loss of p rotein function, providing strong evidence that ALS2 is the causative gene underlying this form of ALS.