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Original Contribution
April 2008

Risk of Parkinson Disease in Carriers of Parkin Mutations: Estimation Using the Kin-Cohort Method

Author Affiliations

Author Affiliations: Departments of Biostatistics (Dr Wang) and Epidemiology (Drs Louis, Andrews, and Ottman), Mailman School of Public Health, New York, New York; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, New York (Drs Clark, Louis, and Marder); Gertrude H. Sergievsky Center, New York (Drs Louis, Cote, Andrews, Ottman, and Marder and Ms Mejia-Santana); Departments of Pathology (Dr Clark), Neurology (Drs Louis, Harris, Cote, Waters, Ford, Frucht, Fahn, Ottman, and Marder), and Psychiatry (Dr Marder), College of Physicians and Surgeons, and Department of Statistics (Dr Rabinowitz), Columbia University, New York; and the Epidemiology of Brain Disorders Department, New York State Psychiatric Institute (Dr Ottman), New York.

Arch Neurol. 2008;65(4):467-474. doi:10.1001/archneur.65.4.467

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 a mutation 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.