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

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

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Chromatography, High Pressure Liquid / methods
  • Cross-Sectional Studies
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Genotype
  • Hispanic Americans / ethnology
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Parkinson Disease / diagnosis*
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • Point Mutation / genetics*
  • Retrospective Studies
  • Risk Factors
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Ubiquitin-Protein Ligases
  • parkin protein