SCA17 repeat expansion: mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications.
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.
Chen
Chiung-Mei
CM
Department of Neurology, Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taipei, Taiwan.
Lee
Li-Ching
LC
Soong
Bing-Wen
BW
Fung
Hon-Chung
HC
Hsu
Wen-Chuin
WC
Lin
Pei-Ying
PY
Huang
Hui-Ju
HJ
Chen
Fen-Lin
FL
Lin
Cheng-Yueh
CY
Lee-Chen
Guey-Jen
GJ
Wu
Yih-Ru
YR
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*
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D035181:TATA-Box Binding Protein; C509817:TBP protein, human