title: Senataxin mutations and amyotrophic lateral sclerosis.
abstract: We studied three patients with mutations in the senataxin gene (SETX). One had juvenile onset of ALS. The second case resembled hereditary motor neuropathy. The third patient had an overlap syndrome of ataxia-tremor and motor neuron disease, phenotypes previously associated with SETX mutations. Our patients were all apparently sporadic, with no other affected relative. Two relatives of patient no. 2 carried the SETX c.4660T > G transversion but did not manifest motor neuron disease, abnormal eye movements, ataxia, or tremor suggesting that genetic or environmental modifiers may influence expression of this SETX polymorphism. Relatives of patients 1 and 3 were not available for examination or SETX mutation screening. Mutations causing ALS4 may be more frequent and heterogeneous than expected. Screening for SETX mutations should be considered in patients with apparently sporadic juvenile-onset ALS, hereditary motor neuropathy, and overlap syndromes with ataxia and motor neuron disease.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA. mh29@columbia.edu
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Quinzii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsumoto
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Hays
authors.forename: J Kirk
authors.initials: JK
authors.lastname: Roberts
authors.forename: Patricia
authors.initials: P
authors.lastname: Richard
authors.forename: Lewis P
authors.initials: LP
authors.lastname: Rowland
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D004265:DNA Helicases; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D064251:Multifunctional Enzymes; D009154:Mutation; D020365:RNA Helicases / Q000235:genetics*; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases