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Multicenter Study
. 2010 Jun;67(6):731-8.
doi: 10.1001/archneurol.2010.95.

Predictors of parkin mutations in early-onset Parkinson disease: the consortium on risk for early-onset Parkinson disease study

Karen S Marder  1 , Ming X Tang, Helen Mejia-Santana, Llency Rosado, Elan D Louis, Cynthia L Comella, Amy Colcher, Andrew D Siderowf, Danna Jennings, Martha A Nance, Susan Bressman, William K Scott, Caroline M Tanner, Susan F Mickel, Howard F Andrews, Cheryl Waters, Stanley Fahn, Barbara M Ross, Lucien J Cote, Steven Frucht, Blair Ford, Roy N Alcalay, Michael Rezak, Kevin Novak, Joseph H Friedman, Ronald F Pfeiffer, Laura Marsh, Brad Hiner, Gregory D Neils, Miguel Verbitsky, Sergey Kisselev, Elise Caccappolo, Ruth Ottman, Lorraine N Clark
Affiliations
Multicenter Study

Predictors of parkin mutations in early-onset Parkinson disease: the consortium on risk for early-onset Parkinson disease study

Karen S Marder et al. Arch Neurol. 2010 Jun.

Abstract

Background: Mutations in the parkin gene are the most common genetic cause of early-onset Parkinson disease (PD). Results from a multicenter study of patients with PD systematically sampled by age at onset have not been reported to date.

Objective: To determine risk factors associated with carrying parkin mutations.

Design: Cross-sectional observational study.

Setting: Thirteen movement disorders centers.

Participants: A total of 956 patients with early-onset PD, defined as age at onset younger than 51 years.

Main outcome measures: Presence of heterozygous, homozygous, or compound heterozygous parkin mutations.

Results: Using a previously validated interview, 14.7% of patients reported a family history of PD in a first-degree relative. Sixty-four patients (6.7%) had parkin mutations (3.9% heterozygous, 0.6% homozygous, and 2.2% compound heterozygous). Copy number variation was present in 52.3% of mutation carriers (31.6% of heterozygous, 83.3% of homozygous, and 81.0% of compound heterozygous). Deletions in exons 3 and 4 and 255delA were common among Hispanics (specifically Puerto Ricans). Younger age at onset (<40 years) (odds ratio [OR], 5.0; 95% confidence interval [CI], 2.8-8.8; P = .001), Hispanic race/ethnicity (OR compared with white non-Hispanic race/ethnicity, 2.7; 95% CI, 1.3-5.7; P = .009), and family history of PD in a first-degree relative (OR compared with noncarriers, 2.8; 95% CI, 1.5-5.3; P = .002) were associated with carrying any parkin mutation (heterozygous, homozygous, or compound heterozygous). Hispanic race/ethnicity was associated with carrying a heterozygous mutation (OR compared with white non-Hispanic race/ethnicity, 2.8; 95% CI, 1.1-7.2; P = .03) after adjustment for covariates.

Conclusions: Age at onset, Hispanic race/ethnicity, and family history of PD are associated with carrying any parkin mutation (heterozygous, homozygous, or compound heterozygous) and heterozygous mutations alone. The increased odds of carrying a parkin mutation among Hispanics warrants further study.

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Conflict of interest statement

Disclosure: The authors report no conflicts of interest.

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