title: Frequency of known mutations in early-onset Parkinson disease: implication for genetic counseling: the consortium on risk for early onset Parkinson disease study.
abstract: OBJECTIVE
  To assess the frequency and clinical characteristics of carriers of previously identified mutations in 6 genes associated with early-onset Parkinson disease (PD) and provide empirical data that can be used to inform genetic counseling.
  
  
  METHODS
  Cross-sectional observational study.
  
  
  METHODS
  Thirteen movement disorders centers.
  
  
  METHODS
  Nine hundred fifty-three individuals with early-onset PD defined as age at onset (AAO) younger than 51 years. Participants included 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Intervention Mutations in SNCA, PRKN, PINK1, DJ1, LRRK2, and GBA were assessed. A validated family history interview and the Unified Parkinson Disease Rating Scale were administered. Demographic and phenotypic characteristics were compared among groups defined by mutation status. Main Outcome Measure Mutation carrier frequency stratified by AAO and ethnic background.
  
  
  RESULTS
  One hundred fifty-eight (16.6%) participants had mutations, including 64 (6.7%) PRKN, 35 (3.6%) LRRK2 G2019S, 64 (6.7%) GBA, and 1 (0.2%) DJ1. Mutation carriers were more frequent in those with an AAO of 30 years or younger compared with those with AAO between 31 and 50 years (40.6% vs 14.6%, P < .001), in individuals who reported Jewish ancestry (32.4% vs 13.7%, P < .001), and in those reporting a first-degree family history of PD (23.9% vs 15.1%, P = .01). Hispanic individuals were more likely to be PRKN carriers than non-Hispanic individuals (15.6% vs 5.9%, P = .003). The GBA L444P mutation was associated with a higher mean Unified Parkinson Disease Rating Scale III score after adjustment for covariates.
  
  
  CONCLUSIONS
  Individuals of Jewish or Hispanic ancestry with early-onset PD, those with AAO of 30 years or younger, and those with a history of PD in a first-degree relative may benefit from genetic counseling.
authors.affiliation: Department of Neurology, Columbia University, New York, NY 10032, USA.
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
authors.forename: Elise
authors.initials: E
authors.lastname: Caccappolo
authors.forename: Helen
authors.initials: H
authors.lastname: Mejia-Santana
authors.forename: Ming Xin
authors.initials: MX
authors.lastname: Tang
authors.forename: Llency
authors.initials: L
authors.lastname: Rosado
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Ross
authors.forename: Miguel
authors.initials: M
authors.lastname: Verbitsky
authors.forename: Sergey
authors.initials: S
authors.lastname: Kisselev
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.forename: Cynthia
authors.initials: C
authors.lastname: Comella
authors.forename: Amy
authors.initials: A
authors.lastname: Colcher
authors.forename: Danna
authors.initials: D
authors.lastname: Jennings
authors.forename: Martha A
authors.initials: MA
authors.lastname: Nance
authors.forename: Susan B
authors.initials: SB
authors.lastname: Bressman
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Caroline
authors.initials: C
authors.lastname: Tanner
authors.forename: Susan
authors.initials: S
authors.lastname: Mickel
authors.forename: Howard
authors.initials: H
authors.lastname: Andrews
authors.forename: Cheryl
authors.initials: C
authors.lastname: Waters
authors.forename: Stanley
authors.initials: S
authors.lastname: Fahn
authors.forename: Lucien
authors.initials: L
authors.lastname: Cote
authors.forename: Steven
authors.initials: S
authors.lastname: Frucht
authors.forename: Blair
authors.initials: B
authors.lastname: Ford
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
authors.initials: R
authors.lastname: Pfeiffer
authors.forename: Laura
authors.initials: L
authors.lastname: Marsh
authors.forename: Bradley
authors.initials: B
authors.lastname: Hiner
authors.forename: Andrew
authors.initials: A
authors.lastname: Siderowf
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
authors.forename: Lorraine N
authors.initials: LN
authors.lastname: Clark
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D012044:Regression Analysis; D012306:Risk; D014481:United States / Q000208:ethnology