title: Novel ATP13A2 variant associated with Parkinson disease in Taiwan and Singapore.
abstract: OBJECTIVE
  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 (18)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.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: C H
authors.initials: CH
authors.lastname: Lin
authors.forename: E K
authors.initials: EK
authors.lastname: Tan
authors.forename: M L
authors.initials: ML
authors.lastname: Chen
authors.forename: L C
authors.initials: LC
authors.lastname: Tan
authors.forename: H Q
authors.initials: HQ
authors.lastname: Lim
authors.forename: G S
authors.initials: GS
authors.lastname: Chen
authors.forename: R M
authors.initials: RM
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000235:genetics; D044466:Asian People / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D006180:Proton-Translocating ATPases / Q000235:genetics*; D012846:Singapore; D013624:Taiwan; D013912:Threonine / Q000235:genetics; D055815:Young Adult
chemical_list: C514983:ATP13A2 protein, human; D013912:Threonine; D006180:Proton-Translocating ATPases; D000409:Alanine