SCA17 repeat expansion: Mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications

Chiung Mei Chen, Li Ching Lee, Bing Wen Soong, Hon Chung Fung, Wen Chuin Hsu, Pei Ying Lin, Hui Ju Huang, Fen Lin Chen, Cheng Yueh Lin, Guey Jen Lee-Chen, Yih Ru Wu

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)375-380
Number of pages6
JournalClinica Chimica Acta
Volume411
Issue number5-6
DOIs
Publication statusPublished - 2010 Mar 2

Fingerprint

TATA-Box Binding Protein
Nervous System Diseases
Alleles
Parkinsonian Disorders
tert-Butylhydroperoxide
Peptide Initiation Factors
General Transcription Factors
Gene encoding
Cell death
Transcription
Protein Isoforms
Genes
Parkinson Disease
Spinocerebellar Ataxia 17
Alzheimer Disease
Cell Death
Phenotype
Mutation

Keywords

  • Clinical study
  • Expression analysis
  • Lymphoblastoid cells
  • SCA17
  • TBP expansion

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Chen, C. M., Lee, L. C., Soong, B. W., Fung, H. C., Hsu, W. C., Lin, P. Y., ... Wu, Y. R. (2010). SCA17 repeat expansion: Mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications. Clinica Chimica Acta, 411(5-6), 375-380. https://doi.org/10.1016/j.cca.2009.12.002

SCA17 repeat expansion : Mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications. / Chen, Chiung Mei; Lee, Li Ching; Soong, Bing Wen; Fung, Hon Chung; Hsu, Wen Chuin; Lin, Pei Ying; Huang, Hui Ju; Chen, Fen Lin; Lin, Cheng Yueh; Lee-Chen, Guey Jen; Wu, Yih Ru.

In: Clinica Chimica Acta, Vol. 411, No. 5-6, 02.03.2010, p. 375-380.

Research output: Contribution to journalArticle

Chen, CM, Lee, LC, Soong, BW, Fung, HC, Hsu, WC, Lin, PY, Huang, HJ, Chen, FL, Lin, CY, Lee-Chen, GJ & Wu, YR 2010, 'SCA17 repeat expansion: Mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications', Clinica Chimica Acta, vol. 411, no. 5-6, pp. 375-380. https://doi.org/10.1016/j.cca.2009.12.002
Chen, Chiung Mei ; Lee, Li Ching ; Soong, Bing Wen ; Fung, Hon Chung ; Hsu, Wen Chuin ; Lin, Pei Ying ; Huang, Hui Ju ; Chen, Fen Lin ; Lin, Cheng Yueh ; Lee-Chen, Guey Jen ; Wu, Yih Ru. / SCA17 repeat expansion : Mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications. In: Clinica Chimica Acta. 2010 ; Vol. 411, No. 5-6. pp. 375-380.
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AU - Fung, Hon Chung

AU - Hsu, Wen Chuin

AU - Lin, Pei Ying

AU - Huang, Hui Ju

AU - Chen, Fen Lin

AU - Lin, Cheng Yueh

AU - Lee-Chen, Guey Jen

AU - Wu, Yih Ru

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AB - 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.

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