title: Predictors of parkin mutations in early-onset Parkinson disease: the consortium on risk for early-onset Parkinson disease study.
abstract: BACKGROUND
  Mutations in the parkin gene are the most common genetic cause of early-onset Parkinson disease (PD). Results from a multicenter study of patients with PD systematically sampled by age at onset have not been reported to date.
  
  
  OBJECTIVE
  To determine risk factors associated with carrying parkin mutations.
  
  
  METHODS
  Cross-sectional observational study.
  
  
  METHODS
  Thirteen movement disorders centers.
  
  
  METHODS
  A total of 956 patients with early-onset PD, defined as age at onset younger than 51 years.
  
  
  METHODS
  Presence of heterozygous, homozygous, or compound heterozygous parkin mutations.
  
  
  RESULTS
  Using a previously validated interview, 14.7% of patients reported a family history of PD in a first-degree relative. Sixty-four patients (6.7%) had parkin mutations (3.9% heterozygous, 0.6% homozygous, and 2.2% compound heterozygous). Copy number variation was present in 52.3% of mutation carriers (31.6% of heterozygous, 83.3% of homozygous, and 81.0% of compound heterozygous). Deletions in exons 3 and 4 and 255delA were common among Hispanics (specifically Puerto Ricans). Younger age at onset (<40 years) (odds ratio [OR], 5.0; 95% confidence interval [CI], 2.8-8.8; P = .001), Hispanic race/ethnicity (OR compared with white non-Hispanic race/ethnicity, 2.7; 95% CI, 1.3-5.7; P = .009), and family history of PD in a first-degree relative (OR compared with noncarriers, 2.8; 95% CI, 1.5-5.3; P = .002) were associated with carrying any parkin mutation (heterozygous, homozygous, or compound heterozygous). Hispanic race/ethnicity was associated with carrying a heterozygous mutation (OR compared with white non-Hispanic race/ethnicity, 2.8; 95% CI, 1.1-7.2; P = .03) after adjustment for covariates.
  
  
  CONCLUSIONS
  Age at onset, Hispanic race/ethnicity, and family history of PD are associated with carrying any parkin mutation (heterozygous, homozygous, or compound heterozygous) and heterozygous mutations alone. The increased odds of carrying a parkin mutation among Hispanics warrants further study.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 630 W 168th St, Unit 16, New York, NY 10032, USA. ksm1@columbia.edu
authors.forename: Karen S
authors.initials: KS
authors.lastname: Marder
authors.forename: Ming X
authors.initials: MX
authors.lastname: Tang
authors.forename: Helen
authors.initials: H
authors.lastname: Mejia-Santana
authors.forename: Llency
authors.initials: L
authors.lastname: Rosado
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Comella
authors.forename: Amy
authors.initials: A
authors.lastname: Colcher
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Siderowf
authors.forename: Danna
authors.initials: D
authors.lastname: Jennings
authors.forename: Martha A
authors.initials: MA
authors.lastname: Nance
authors.forename: Susan
authors.initials: S
authors.lastname: Bressman
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Tanner
authors.forename: Susan F
authors.initials: SF
authors.lastname: Mickel
authors.forename: Howard F
authors.initials: HF
authors.lastname: Andrews
authors.forename: Cheryl
authors.initials: C
authors.lastname: Waters
authors.forename: Stanley
authors.initials: S
authors.lastname: Fahn
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Ross
authors.forename: Lucien J
authors.initials: LJ
authors.lastname: Cote
authors.forename: Steven
authors.initials: S
authors.lastname: Frucht
authors.forename: Blair
authors.initials: B
authors.lastname: Ford
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
authors.forename: Michael
authors.initials: M
authors.lastname: Rezak
authors.forename: Kevin
authors.initials: K
authors.lastname: Novak
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Friedman
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Pfeiffer
authors.forename: Laura
authors.initials: L
authors.lastname: Marsh
authors.forename: Brad
authors.initials: B
authors.lastname: Hiner
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Neils
authors.forename: Miguel
authors.initials: M
authors.lastname: Verbitsky
authors.forename: Sergey
authors.initials: S
authors.lastname: Kisselev
authors.forename: Elise
authors.initials: E
authors.lastname: Caccappolo
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
authors.forename: Lorraine N
authors.initials: LN
authors.lastname: Clark
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006630:Hispanic or Latino / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein