title: A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2.
abstract: Amyotrophic lateral sclerosis 2 (ALS2) is an autosomal recessive form of juvenile 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 frameshifts that generate premature stop codons. ALS2 is expressed in various tissues and cells, including neurons throughout the brain and spinal cord, and encodes a protein containing multiple domains that have homology to RanGEF as well as RhoGEF. Deletion mutations are predicted to cause a loss of protein function, providing strong evidence that ALS2 is the causative gene underlying this form of ALS.
authors.affiliation: NeuroGenes, International Cooperative Research Project, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hadano
authors.forename: C K
authors.initials: CK
authors.lastname: Hand
authors.forename: H
authors.initials: H
authors.lastname: Osuga
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: A
authors.initials: A
authors.lastname: Otomo
authors.forename: R S
authors.initials: RS
authors.lastname: Devon
authors.forename: N
authors.initials: N
authors.lastname: Miyamoto
authors.forename: J
authors.initials: J
authors.lastname: Showguchi-Miyata
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: R
authors.initials: R
authors.lastname: Singaraja
authors.forename: D A
authors.initials: DA
authors.lastname: Figlewicz
authors.forename: T
authors.initials: T
authors.lastname: Kwiatkowski
authors.forename: B A
authors.initials: BA
authors.lastname: Hosler
authors.forename: T
authors.initials: T
authors.lastname: Sagie
authors.forename: J
authors.initials: J
authors.lastname: Skaug
authors.forename: J
authors.initials: J
authors.lastname: Nasir
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
authors.forename: S W
authors.initials: SW
authors.lastname: Scherer
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
authors.forename: J E
authors.initials: JE
authors.lastname: Ikeda
mesh_terms: D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid
chemical_list: C438187:ALS2 protein, human; D020662:Guanine Nucleotide Exchange Factors; D020558:GTP Phosphohydrolases