ATP13A2 variability in Taiwanese Parkinson's disease

Chiung Mei Chen, Chih Hsin Lin, Hsueh Fen Juan, Fen Ju Hu, Ya Chin Hsiao, Hsin Yi Chang, Chih Ying Chao, I. Cheng Chen, Li Ching Lee, Tsu Wei Wang, Ya Tang Chen, Yi Tsun Chen, Guey Jen Lee-Chen*, Yih Ru Wu


研究成果: 雜誌貢獻期刊論文同行評審

18 引文 斯高帕斯(Scopus)


Mutations in ATP13A2 have been reported to associate with Parkinson's disease (PD). This study investigates the contribution of genetic variants in ATP13A2 to Taiwanese PD. ATP13A2 cDNA fragments from 65 early onset PD (onset <50 years) were sequenced. The identified variants were validated in a cohort of PD (n=493) and ethnically matched controls (n=585). A novel heterozygous G1014S, located at the conserved seventh transmembrane domain of ATP13A2 protein, was identified in an early onset PD patient, which was absent in 585 normal controls. Additionally, a reported heterozygous A746T was found in two PD patients and four controls. The clinical features and 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) image of the patients carrying G1014S and A746T were similar to that of idiopathic PD. One normal control with A746T showed an asymmetric reduction of 99mT TRODAT-1 uptake in the right striatum. Under oxidative stress or apoptotic stimulus, lymphoblastoid cells carrying either A764T or G1014S showed increased caspase 3 activity compared with the controls. The rates of decay for G1014S and A746T proteins were more or less reduced in cycloheximide chase experiment. In silico modeling of G1014S exhibited a more stable feature than wild-type, and G1014S is mislocalized mainly in the intralysosomal space, which is coherent with the prediction of prohibiting N-myristoylation and membrane association. We therefore hypothesize that rare variants of ATP13A2 may contribute to PD susceptibility in Taiwan. The role played by ATP13A2 variants in PD remains to be clarified.

頁(從 - 到)720-729
期刊American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
出版狀態已發佈 - 2011 9月

ASJC Scopus subject areas

  • 遺傳學(臨床)
  • 精神病學和心理健康
  • 細胞與分子神經科學


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