Novel ATP13A2 variant associated with Parkinson disease in Taiwan and Singapore
Journal
Neurology
Journal Volume
71
Journal Issue
21
Pages
1727-1732
Date Issued
2008
Author(s)
Abstract
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 F-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. ? 2008 by AAN Enterprises, Inc.
SDGs
Other Subjects
6 fluorodopa f 18; alanine; ATP13A2 protein, human; proton transporting adenosine triphosphatase; threonine; unclassified drug; adolescent; adult; aged; article; ATP13A2 gene; Chinese; controlled study; disease association; ethnicity; exon; female; gene; gene mutation; gene sequence; genetic association; genetic variability; heterozygote; human; intron; major clinical study; male; missense mutation; nucleotide sequence; Parkinson disease; phenotype; phosphorylation; positron emission tomography; priority journal; protein domain; risk factor; screening; Singapore; Taiwan; validity; Asian; chemical structure; gene frequency; genetic predisposition; genetics; genotype; methodology; middle aged; mutation; pathology; Adolescent; Adult; Aged; Aged, 80 and over; Alanine; Asian Continental Ancestry Group; DNA Mutational Analysis; Exons; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Models, Molecular; Mutation; Parkinson Disease; Positron-Emission Tomography; Proton-Translocating ATPases; Singapore; Taiwan; Threonine; Young Adult
Publisher
Lippincott Williams and Wilkins
Type
journal article