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Predictors of Parkin Mutations in Early-Onset Parkinson Disease

2010; American Medical Association; Volume: 67; Issue: 6 Linguagem: Inglês

10.1001/archneurol.2010.95

1538-3687

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

RNA regulation and disease

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.