title: DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4).
abstract: Juvenile amyotrophic lateral sclerosis (ALS4) is a rare autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS) characterized by distal muscle weakness and atrophy, normal sensation, and pyramidal signs. Individuals affected with ALS4 usually have an onset of symptoms at age <25 years, a slow rate of progression, and a normal life span. The ALS4 locus maps to a 1.7-Mb interval on chromosome 9q34 flanked by D9S64 and D9S1198. To identify the molecular basis of ALS4, we tested 19 genes within the ALS4 interval and detected missense mutations (T3I, L389S, and R2136H) in the Senataxin gene (SETX). The SETX gene encodes a novel 302.8-kD protein. Although its function remains unknown, SETX contains a DNA/RNA helicase domain with strong homology to human RENT1 and IGHMBP2, two genes encoding proteins known to have roles in RNA processing. These observations of ALS4 suggest that mutations in SETX may cause neuronal degeneration through dysfunction of the helicase activity or other steps in RNA processing.
authors.affiliation: Division of Genetics and Developmental Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ying-Zhang
authors.initials: YZ
authors.lastname: Chen
authors.forename: Craig L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Huy M
authors.initials: HM
authors.lastname: Huynh
authors.forename: Ian P
authors.initials: IP
authors.lastname: Blair
authors.forename: Imke
authors.initials: I
authors.lastname: Puls
authors.forename: Joy
authors.initials: J
authors.lastname: Irobi
authors.forename: Ines
authors.initials: I
authors.lastname: Dierick
authors.forename: Annette
authors.initials: A
authors.lastname: Abel
authors.forename: Marina L
authors.initials: ML
authors.lastname: Kennerson
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Rabin
authors.forename: Garth A
authors.initials: GA
authors.lastname: Nicholson
authors.forename: Michaela
authors.initials: M
authors.lastname: Auer-Grumbach
authors.forename: Klaus
authors.initials: K
authors.lastname: Wagner
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: John W
authors.initials: JW
authors.lastname: Griffin
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Fischbeck
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: David R
authors.initials: DR
authors.lastname: Cornblath
authors.forename: Phillip F
authors.initials: PF
authors.lastname: Chance
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D001344:Autopsy; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004265:DNA Helicases; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D006822:Hybrid Cells; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D064251:Multifunctional Enzymes; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D020365:RNA Helicases / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D064251:Multifunctional Enzymes; D004247:DNA; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases