title: Risk of Parkinson disease in carriers of parkin mutations: estimation using the kin-cohort method.
abstract: OBJECTIVE
  To estimate the risk of Parkinson disease (PD) in individuals with mutations in the Parkin gene.
  
  
  METHODS
  We assessed point mutations and exon deletions and duplications in the Parkin gene in 247 probands with PD (age at onset < or =50 years) and 104 control probands enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. For each first-degree relative, a consensus diagnosis of PD was established. The probability that each relative carried a mutation was estimated from the proband's Parkin carrier status using Mendelian principles and from the relationship of the relative to the proband.
  
  
  METHODS
  Tertiary care movement disorders center. Patients Cases, controls, and their first-degree relatives were enrolled in the GEPD study.
  
  
  METHODS
  Estimated age-specific penetrance in first-degree relatives.
  
  
  RESULTS
  Parkin mutations were identified in 25 probands with PD (10.1%), 18 (72.0%) of whom were heterozygotes. One Parkin homozygote was reported in 2 siblings with PD. The cumulative incidence of PD to age 65 years in carrier relatives (age-specific penetrance) was estimated to be 7.0% (95% confidence interval, 0.4%-71.9%), compared with 1.7% (95% confidence interval, 0.8%-3.4%) in noncarrier relatives of the cases (P = .59) and 1.1% (95% confidence interval, 0.3%-3.4%) in relatives of the controls (compared with noncarrier relatives, P = .52).
  
  
  CONCLUSIONS
  The cumulative risk of PD to age 65 years in a noncarrier relative of a case with an age at onset of 50 years or younger is not significantly greater than the general population risk among controls. Age-specific penetrance among Parkin carriers, in particular heterozygotes, deserves further study.
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, New York, New York, USA.
authors.forename: Yuanjia
authors.initials: Y
authors.lastname: Wang
authors.forename: Lorraine N
authors.initials: LN
authors.lastname: Clark
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.forename: Helen
authors.initials: H
authors.lastname: Mejia-Santana
authors.forename: Juliette
authors.initials: J
authors.lastname: Harris
authors.forename: Lucien J
authors.initials: LJ
authors.lastname: Cote
authors.forename: Cheryl
authors.initials: C
authors.lastname: Waters
authors.forename: Howard
authors.initials: H
authors.lastname: Andrews
authors.forename: Blair
authors.initials: B
authors.lastname: Ford
authors.forename: Steven
authors.initials: S
authors.lastname: Frucht
authors.forename: Stanley
authors.initials: S
authors.lastname: Fahn
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
authors.forename: Daniel
authors.initials: D
authors.lastname: Rabinowitz
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D015994:Incidence; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D019683:Penetrance; D011336:Probability; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D018570:Risk Assessment
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases