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NEUROLOGY 2008;71:1727-1732
© 2008 American Academy of Neurology

Novel ATP13A2 variant associated with Parkinson disease in Taiwan and Singapore

C. H. Lin, MD, E. K. Tan, MD, M. L. Chen, MSc, L. C. Tan, MD, H. Q. Lim, BSc, G. S. Chen, PhD and R. M. Wu, MD, PhD

From the Department of Neurology (C.H.L., M.L.C., R.M.W.), National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei; Department of Neurology (E.K.T., L.C.T., H.Q.L.), National Neuroscience Institute, Singapore; Department of Applied Chemistry (G.S.C.), Providence University, Sha-Lu, Taiwan; and Duke-NUS Graduate Medical School (E.K.T.), Singapore.

Address correspondence and reprint requests to Dr. Ruey-Meei Wu, Department of Neurology, National Taiwan University Hospital, Taipei 100, Taiwan robinwu{at}ntu.edu.tw.

Objectives: To assess the association of ATP13A2 gene mutation among patients with early onset Parkinson disease (EOPD, onset < 50 years) in ethnic Chinese population.

Methods: Among 771 subjects, we studied 182 patients with EOPD and familial PD and 589 matched controls from two cohorts of Han Chinese in Taiwan and Singapore. The entire ATP13A2 coding region and intron-exon boundaries were sequenced in 71 probands and 70 controls in Taiwanese/ethnic Chinese. An additional 111 index patients with PD in Singapore and 589 controls were later screened to validate possible mutations that were found in the first set of study subjects.

Results: We identified one novel missense variant, AL746Thr, in a single heterozygous state in three patients (two were from Taiwan and one was from Singapore) (1.7% in EOPD). The variant was not observed in 589 ethnicity matched controls. The frequency of this variant was significantly higher in PD cases than controls (p = 0.01, relative risk 4.3, 95% CI 1.9–4.3). The clinical phenotype and 18F-dopa PET image of ATP13A2 Ala78Thr carriers are similar to that seen in idiopathic PD. The variant is located between the highly conserved phosphorylation region and the fifth transmembrane domain of the ATP13A2 protein.

Conclusions: A rare variant of the ATP13A2 was associated with an increased risk of Parkinson disease among ethnic Chinese in Asia. Further studies are needed to clarify the functional role of this genetic risk factor.

GLOSSARY: cDNA = complementary DNA; EOPD = early onset Parkinson disease; ER = endoplasmic reticulum; RT-PCR = reverse-transcriptase PCR; SNP = single nucleotide polymorphism.

Supplemental data at www.neurology.org

*These authors contributed equally.

Supported by The National Taiwan University Hospital (97-N-979), National Medical Research Council and Biomedical Research Council, Singapore, and Duke-NUS Graduate Medical School.

Disclosure: The authors report no disclosures.

Received April 28, 2008. Accepted in final form August 19, 2008.






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