title: The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).
authors.affiliation: Department of Neurology, Northwestern University Medical School, Chicago, Illinois, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: A
authors.initials: A
authors.lastname: Hentati
authors.forename: H X
authors.initials: HX
authors.lastname: Deng
authors.forename: O
authors.initials: O
authors.lastname: Dabbagh
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: W Y
authors.initials: WY
authors.lastname: Hung
authors.forename: K
authors.initials: K
authors.lastname: Ouahchi
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.forename: A C
authors.initials: AC
authors.lastname: Azim
authors.forename: N
authors.initials: N
authors.lastname: Cole
authors.forename: G
authors.initials: G
authors.lastname: Gascon
authors.forename: A
authors.initials: A
authors.lastname: Yagmour
authors.forename: M
authors.initials: M
authors.lastname: Ben-Hamida
authors.forename: M
authors.initials: M
authors.lastname: Pericak-Vance
authors.forename: F
authors.initials: F
authors.lastname: Hentati
authors.forename: T
authors.initials: T
authors.lastname: Siddique
mesh_terms: D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: C438187:ALS2 protein, human; D017931:DNA Primers; D020662:Guanine Nucleotide Exchange Factors