title: Single-nucleotide polymorphisms in uncoding regions of ALS2 gene of Japanese patients with autosomal-recessive amyotrophic lateral sclerosis.
abstract: ALS2 is an autosomal recessive form of amyotrophic lateral sclerosis (AR-ALS) with juvenile onset, and has been mostly found in North African and Middle Eastern countries. Deletion mutations in the coding exons of a new gene ALS2, encoding a protein with guanine-nucleotide exchange factor (GEF) domains, have recently been identified in ALS2 patients. These mutations are predicted to cause a loss of protein function, indicating that ALS2 is the causative gene underlying ALS2. To examine whether ALS2 is mutated in Japanese ALS patients sharing some characteristics of ALS2, we analyzed ALS2 gene from three patients with AR-ALS. While no deletion mutation was detected in the coding regions of ALS2 gene, several single-nucleotide polymorphisms (SNPs) that have been found in healthy controls as well as in Tunisian ALS2 patients were found mostly in intronic regions of the gene. These results suggest that deletion mutations in ALS2 gene detected in ALS2 patients seem to be uncommon in Japanese AR-ALS, and that SNPs in uncoding regions might possibly be relevant to predisposition to ALS.
authors.affiliation: Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan. inagano@cc.okayama-u.ac.jp
authors.forename: Isao
authors.initials: I
authors.lastname: Nagano
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Murakami
authors.forename: Mito
authors.initials: M
authors.lastname: Shiote
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Manabe
authors.forename: Shinji
authors.initials: S
authors.lastname: Hadano
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: Joh-E
authors.initials: JE
authors.lastname: Ikeda
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007438:Introns; D007564:Japan; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: C438187:ALS2 protein, human; D020662:Guanine Nucleotide Exchange Factors