Predictors of Parkin mutations in early-onset Parkinson disease: The consortium on risk for early-onset Parkinson disease study

Karen S. Marder, 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 FruchtBlair 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

Research output: Contribution to journalArticle

57 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)731-738
Number of pages8
JournalArchives of neurology
Volume67
Issue number6
DOIs
StatePublished - Jun 2010

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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