title: Exome analysis reveals a Japanese family with spinocerebellar ataxia, autosomal recessive 1.
abstract: Spinocerebellar ataxia autosomal recessive 1 (SCAR1/AOA2) is clinically characterized by an early-onset progressive cerebellar ataxia with axonal neuropathy, ocular motor apraxia, and elevation of serum alpha-fetoprotein level. The disorder is caused by mutations in senataxin (SETX) gene. Here, we report a Japanese SCAR1/AOA2 family with a homozygous nonsense mutation (p.Q1441X) of SETX that was identified by exome sequencing. The family was previously reported as early-onset ataxia of undetermined cause. The present study emphasized the role of whole exome-sequence analysis to establish the molecular diagnosis of neurodegenerative disease presenting with diverse clinical presentations.
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Yaeko
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishiura
authors.forename: Jun
authors.initials: J
authors.lastname: Mitsui
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takuma
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kanazawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Doi
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshimura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morishita
authors.forename: Jun
authors.initials: J
authors.lastname: Goto
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D004265:DNA Helicases; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007564:Japan; D008297:Male; D064251:Multifunctional Enzymes; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020365:RNA Helicases / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000151:congenital; D013132:Spinocerebellar Degenerations / Q000235:genetics*
chemical_list: D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases
keywords: Alpha-fetoprotein; Autosomal recessive 1; Exome analysis; Exon capture; Linkage analysis; Massively parallel sequencing; SETX; Spinocerebellar ataxia