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

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 ( 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.