Mutation screening of the ALS2 gene in sporadic and familial amyotrophic lateral sclerosis

Background: Mutations in the ALS2 gene cause juvenile-onset autosomal recessive amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia. Objective: To assess the role of ALS2 among more common forms of ALS. Methods: DNA from 95 unrelated familial, 95 unrelated sporadic, and 11 early-onset ALS patients was screened for mutations in ALS2 by denaturing high-performance liquid chromatography and direct sequencing of polymerase chain reaction-amplified fragments. Each variant identified was also analyzed among control subjects. All 34 exons of ALS2 plus the 5' and 3'-untranslated region were screened. Results: We detected 23 novel sequence variants; however, none is disease-associated. Conclusion: Mutations of ALS2 are not a common cause of ALS.