Risk of Parkinson disease in carriers of Parkin mutations: Estimation using the kin-cohort method

Yuanjia Wang, Lorraine N. Clark, Elan D. Louis, Helen Mejia-Santana, Juliette Harris, Lucien J. Cote, Cheryl Waters, Howard Andrews, Blair Ford, Steven Frucht, Stanley Fahn, Ruth Ottman, Daniel Rabinowitz, Karen Marder

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Objective: To estimate the risk of Parkinson disease (PD) in individuals with mutations in the Parkin gene. Design: We assessed point mutations and exon deletions and duplications in the Parkin gene in 247 probands with PD (age at onset ≤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 amutation was estimated from the proband's Parkin carrier status using Mendelian principles and from the relationship of the relative to the proband. Setting: Tertiary care movement disorders center. Patients: Cases, controls, and their first-degree relatives were enrolled in the GEPD study. Main Outcome Measures: 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.

Original languageEnglish (US)
Pages (from-to)467-474
Number of pages8
JournalArchives of neurology
Issue number4
StatePublished - Apr 2008
Externally publishedYes

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology


Dive into the research topics of 'Risk of Parkinson disease in carriers of Parkin mutations: Estimation using the kin-cohort method'. Together they form a unique fingerprint.

Cite this