TY - JOUR
T1 - Predictors of Parkin mutations in early-onset Parkinson disease
T2 - The consortium on risk for early-onset Parkinson disease study
AU - Marder, Karen S.
AU - Tang, Ming X.
AU - Mejia-Santana, Helen
AU - Rosado, Llency
AU - Louis, Elan D.
AU - Comella, Cynthia L.
AU - Colcher, Amy
AU - Siderowf, Andrew D.
AU - Jennings, Danna
AU - Nance, Martha A.
AU - Bressman, Susan
AU - Scott, William K.
AU - Tanner, Caroline M.
AU - Mickel, Susan F.
AU - Andrews, Howard F.
AU - Waters, Cheryl
AU - Fahn, Stanley
AU - Ross, Barbara M.
AU - Cote, Lucien J.
AU - Frucht, Steven
AU - Ford, Blair
AU - Alcalay, Roy N.
AU - Rezak, Michael
AU - Novak, Kevin
AU - Friedman, Joseph H.
AU - Pfeiffer, Ronald F.
AU - Marsh, Laura
AU - Hiner, Brad
AU - Neils, Gregory D.
AU - Verbitsky, Miguel
AU - Kisselev, Sergey
AU - Caccappolo, Elise
AU - Ottman, Ruth
AU - Clark, Lorraine N.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77953633735&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953633735&partnerID=8YFLogxK
U2 - 10.1001/archneurol.2010.95
DO - 10.1001/archneurol.2010.95
M3 - Article
C2 - 20558392
AN - SCOPUS:77953633735
SN - 0003-9942
VL - 67
SP - 731
EP - 738
JO - Archives of Neurology
JF - Archives of Neurology
IS - 6
ER -