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.
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.
Authors: Martin Kann; Helfried Jacobs; Kathrin Mohrmann; Kirsten Schumacher; Katja Hedrich; Jennifer Garrels; Karin Wiegers; Eberhard Schwinger; Peter P Pramstaller; Xandra O Breakefield; Laurie J Ozelius; Peter Vieregge; Christine Klein Journal: Ann Neurol Date: 2002-05 Impact factor: 10.422
Authors: T Kitada; S Asakawa; N Hattori; H Matsumine; Y Yamamura; S Minoshima; M Yokochi; Y Mizuno; N Shimizu Journal: Nature Date: 1998-04-09 Impact factor: 49.962
Authors: T Foroud; S K Uniacke; L Liu; N Pankratz; A Rudolph; C Halter; C Shults; K Marder; P M Conneally; W C Nichols Journal: Neurology Date: 2003-03-11 Impact factor: 9.910
Authors: N Abbas; C B Lücking; S Ricard; A Dürr; V Bonifati; G De Michele; S Bouley; J R Vaughan; T Gasser; R Marconi; E Broussolle; C Brefel-Courbon; B S Harhangi; B A Oostra; E Fabrizio; G A Böhme; L Pradier; N W Wood; A Filla; G Meco; P Denefle; Y Agid; A Brice Journal: Hum Mol Genet Date: 1999-04 Impact factor: 6.150
Authors: M X Tang; Y Stern; K Marder; K Bell; B Gurland; R Lantigua; H Andrews; L Feng; B Tycko; R Mayeux Journal: JAMA Date: 1998-03-11 Impact factor: 56.272
Authors: Sofia A Oliveira; William K Scott; Eden R Martin; Martha A Nance; Ray L Watts; Jean P Hubble; William C Koller; Rajesh Pahwa; Matthew B Stern; Bradley C Hiner; William G Ondo; Fred H Allen; Burton L Scott; Christopher G Goetz; Gary W Small; Frank Mastaglia; Jeffrey M Stajich; Fengyu Zhang; Michael W Booze; Michelle P Winn; Lefkos T Middleton; Jonathan L Haines; Margaret A Pericak-Vance; Jeffery M Vance Journal: Ann Neurol Date: 2003-05 Impact factor: 10.422
Authors: E Muñoz; E Tolosa; P Pastor; M J Martí; F Valldeoriola; J Campdelacreu; R Oliva Journal: J Neurol Neurosurg Psychiatry Date: 2002-11 Impact factor: 10.154
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