title: Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease.
abstract: OBJECTIVE
  To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype.
  
  
  METHODS
  Cross-sectional observational study.
  
  
  METHODS
  Thirteen movement disorders centers.
  
  
  METHODS
  Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years.
  
  
  METHODS
  LRRK2 mutation status and Parkinson disease motor phenotype: tremor dominant or PIGD. Demographic information, family history of Parkinson disease, and the Unified Parkinson's Disease Rating Scale score were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C, and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish ancestry, levodopa dose, and family history of Parkinson disease.
  
  
  RESULTS
  Thirty-four cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be Ashkenazi Jewish (55.9% vs 11.9%; P < .001) but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (P = .03) and were more likely to have a PIGD phenotype (92.3% vs 58.9%; P = .003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and Ashkenazi Jewish ancestry (odds ratio, 17.7; P < .001).
  
  
  CONCLUSIONS
  Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course.
authors.affiliation: Department of Neurology, Columbia University, New York, NY 10032, USA.
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
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: Miguel
authors.initials: M
authors.lastname: Verbitsky
authors.forename: Sergey
authors.initials: S
authors.lastname: Kisselev
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Ross
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: 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
authors.initials: C
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 H
authors.initials: CH
authors.lastname: Waters
authors.forename: Stanley
authors.initials: S
authors.lastname: Fahn
authors.forename: Lucien J
authors.initials: LJ
authors.lastname: Cote
authors.forename: Steven J
authors.initials: SJ
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: 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
authors.forename: Karen S
authors.initials: KS
authors.lastname: Marder
mesh_terms: D000328:Adult; D017668:Age of Onset; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D019957:Motor Skills Disorders / Q000235:genetics* / Q000503:physiopathology; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases