title: SCA17 repeat expansion: mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications.
abstract: BACKGROUND
  Spinocerebellar ataxia type 17 (SCA17) involves the expression of a CAG/CAA expansion mutation in the gene encoding TATA-box binding protein (TBP), a general transcription initiation factor. The spectrum of SCA17 clinical presentation is broad.
  
  
  METHODS
  We screened for triplet expansion in the TBP gene in Taiwanese Parkinson's disease (PD), Alzheimer's disease (AD) and atypical parkinsonism and investigated the functional implication of expanded alleles using lymphoblastoid cells as a model.
  
  
  RESULTS
  A total of 6 mildly expanded alleles (44-46) were identified in patients group. The frequency of the individuals carrying expanded alleles in PD (3/602 [0.5%]), AD (2/245 [0.8%]) and atypical parkinsonism (1/44 [2.3%]) is not significant as compared to that in the control subjects (0/644 [0.0%]). In lymphoblastoid cells, HSPA5, HSPA8 and HSPB1 expression levels in cells with expanded TBP were significantly lower than that of the control cells. Although not significantly, the levels of PARK7 protein isoforms 6.1 and 6.4 are notably increased in SCA17 lymphoblastoid cells. Treatment of TBH (tert-butyl hydroperoxide) significantly increases cell death in the cells with mildly expanded TBP.
  
  
  CONCLUSIONS
  Our findings expand the spectrum of SCA17 phenotype and may contribute to our understanding of the disease.
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taipei, Taiwan.
authors.forename: Chiung-Mei
authors.initials: CM
authors.lastname: Chen
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Lee
authors.forename: Bing-Wen
authors.initials: BW
authors.lastname: Soong
authors.forename: Hon-Chung
authors.initials: HC
authors.lastname: Fung
authors.forename: Wen-Chuin
authors.initials: WC
authors.lastname: Hsu
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Lin
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Huang
authors.forename: Fen-Lin
authors.initials: FL
authors.lastname: Chen
authors.forename: Cheng-Yueh
authors.initials: CY
authors.lastname: Lin
authors.forename: Guey-Jen
authors.initials: GJ
authors.lastname: Lee-Chen
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Wu
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D002460:Cell Line; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D012680:Sensitivity and Specificity; D035181:TATA-Box Binding Protein / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D035181:TATA-Box Binding Protein; C509817:TBP protein, human