title: In cis autosomal dominant mutation of Senataxin associated with tremor/ataxia syndrome.
abstract: Senataxin mutations are the molecular basis of two distinct syndromes: (1) ataxia oculomotor apraxia type 2 (AOA2) and (2) juvenile amyotrophic lateral sclerosis 4 (ALS4). The authors describe clinical and molecular genetic studies of mother and daughter who display symptoms of cerebellar ataxia/atrophy, oculomotor defects, and tremor. Both patients share Senataxin mutations N603D and Q653K in cis (N603D-Q653K), adjacent to an N-terminal domain thought to function in protein-protein interaction. The N-terminal and helicase domains appear to harbor missense mutation clusters associated with AOA2 and ALS4. Working synergistically, the N603D-Q653K mutations may confer a partial dominant negative effect, acting on the senataxin N-terminal, further expanding the phenotypic spectrum associated with Senataxin mutations.
authors.affiliation: Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Bassuk
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Chen
authors.forename: S D
authors.initials: SD
authors.lastname: Batish
authors.forename: N
authors.initials: N
authors.lastname: Nagan
authors.forename: P
authors.initials: P
authors.lastname: Opal
authors.forename: P F
authors.initials: PF
authors.lastname: Chance
authors.forename: C L
authors.initials: CL
authors.lastname: Bennett
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D001259:Ataxia / Q000235:genetics*; D004265:DNA Helicases; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D064251:Multifunctional Enzymes; D009154:Mutation; D010375:Pedigree; D020365:RNA Helicases / Q000235:genetics*; D013577:Syndrome; D014202:Tremor / Q000235:genetics*
chemical_list: D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases