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.


METHODS
Cross-sectional observational study.


METHODS
Thirteen movement disorders centers.


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


METHODS
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.
Marder
Karen S
KS
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 630 W 168th St, Unit 16, New York, NY 10032, USA. ksm1@columbia.edu
Tang
Ming X
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Mejia-Santana
Helen
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Rosado
Llency
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Louis
Elan D
ED
Comella
Cynthia L
CL
Colcher
Amy
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Siderowf
Andrew D
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Jennings
Danna
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Nance
Martha A
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Bressman
Susan
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Scott
William K
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Tanner
Caroline M
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Mickel
Susan F
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Andrews
Howard F
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Waters
Cheryl
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Fahn
Stanley
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Ross
Barbara M
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Cote
Lucien J
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Frucht
Steven
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Ford
Blair
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Alcalay
Roy N
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Rezak
Michael
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Novak
Kevin
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Friedman
Joseph H
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Pfeiffer
Ronald F
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Marsh
Laura
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Hiner
Brad
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Neils
Gregory D
GD
Verbitsky
Miguel
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Kisselev
Sergey
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Caccappolo
Elise
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Ottman
Ruth
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Clark
Lorraine N
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D000328:Adult; D017668:Age of Onset; D000368:Aged; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006630:Hispanic or Latino / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein