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 Frucht & 14 others Blair 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

50 Citations (Scopus)

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
Pages (from-to)731-738
Number of pages8
JournalArchives of Neurology
Volume67
Issue number6
DOIs
StatePublished - Jun 1 2010

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Parkinson Disease
Mutation
Hispanic Americans
Age of Onset
Odds Ratio
Confidence Intervals
Predictors
Parkinson's Disease
Onset
Movement Disorders
Multicenter Studies
Observational Studies
Exons
Cross-Sectional Studies
Outcome Assessment (Health Care)
Ethnic Groups
Interviews
Confidence Interval
Genes

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Marder, K. S., Tang, M. X., Mejia-Santana, H., Rosado, L., Louis, E. D., Comella, C. L., ... Clark, L. N. (2010). Predictors of Parkin mutations in early-onset Parkinson disease: The consortium on risk for early-onset Parkinson disease study. Archives of Neurology, 67(6), 731-738. https://doi.org/10.1001/archneurol.2010.95

Predictors of Parkin mutations in early-onset Parkinson disease : The consortium on risk for early-onset Parkinson disease study. / Marder, Karen S.; Tang, Ming X.; Mejia-Santana, Helen; Rosado, Llency; Louis, Elan D.; Comella, Cynthia L.; Colcher, Amy; Siderowf, Andrew D.; Jennings, Danna; Nance, Martha A.; Bressman, Susan; Scott, William K; Tanner, Caroline M.; Mickel, Susan F.; Andrews, Howard F.; Waters, Cheryl; Fahn, Stanley; Ross, Barbara M.; Cote, Lucien J.; Frucht, Steven; Ford, Blair; Alcalay, Roy N.; Rezak, Michael; Novak, Kevin; Friedman, Joseph H.; Pfeiffer, Ronald F.; Marsh, Laura; Hiner, Brad; Neils, Gregory D.; Verbitsky, Miguel; Kisselev, Sergey; Caccappolo, Elise; Ottman, Ruth; Clark, Lorraine N.

In: Archives of Neurology, Vol. 67, No. 6, 01.06.2010, p. 731-738.

Research output: Contribution to journalArticle

Marder, KS, Tang, MX, Mejia-Santana, H, Rosado, L, Louis, ED, Comella, CL, Colcher, A, Siderowf, AD, Jennings, D, Nance, MA, Bressman, S, Scott, WK, Tanner, CM, Mickel, SF, Andrews, HF, Waters, C, Fahn, S, Ross, BM, Cote, LJ, Frucht, S, Ford, B, Alcalay, RN, Rezak, M, Novak, K, Friedman, JH, Pfeiffer, RF, Marsh, L, Hiner, B, Neils, GD, Verbitsky, M, Kisselev, S, Caccappolo, E, Ottman, R & Clark, LN 2010, 'Predictors of Parkin mutations in early-onset Parkinson disease: The consortium on risk for early-onset Parkinson disease study', Archives of Neurology, vol. 67, no. 6, pp. 731-738. https://doi.org/10.1001/archneurol.2010.95
Marder, Karen S. ; Tang, Ming X. ; Mejia-Santana, Helen ; Rosado, Llency ; Louis, Elan D. ; Comella, Cynthia L. ; Colcher, Amy ; Siderowf, Andrew D. ; Jennings, Danna ; Nance, Martha A. ; Bressman, Susan ; Scott, William K ; Tanner, Caroline M. ; Mickel, Susan F. ; Andrews, Howard F. ; Waters, Cheryl ; Fahn, Stanley ; Ross, Barbara M. ; Cote, Lucien J. ; Frucht, Steven ; Ford, Blair ; Alcalay, Roy N. ; Rezak, Michael ; Novak, Kevin ; Friedman, Joseph H. ; Pfeiffer, Ronald F. ; Marsh, Laura ; Hiner, Brad ; Neils, Gregory D. ; Verbitsky, Miguel ; Kisselev, Sergey ; Caccappolo, Elise ; Ottman, Ruth ; Clark, Lorraine N. / Predictors of Parkin mutations in early-onset Parkinson disease : The consortium on risk for early-onset Parkinson disease study. In: Archives of Neurology. 2010 ; Vol. 67, No. 6. pp. 731-738.
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title = "Predictors of Parkin mutations in early-onset Parkinson disease: The consortium on risk for early-onset Parkinson disease study",
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.",
author = "Marder, {Karen S.} and Tang, {Ming X.} and Helen Mejia-Santana and Llency Rosado and Louis, {Elan D.} and Comella, {Cynthia L.} and Amy Colcher and Siderowf, {Andrew D.} and Danna Jennings and Nance, {Martha A.} and Susan Bressman and Scott, {William K} and Tanner, {Caroline M.} and Mickel, {Susan F.} and Andrews, {Howard F.} and Cheryl Waters and Stanley Fahn and Ross, {Barbara M.} and Cote, {Lucien J.} and Steven Frucht and Blair Ford and Alcalay, {Roy N.} and Michael Rezak and Kevin Novak and Friedman, {Joseph H.} and Pfeiffer, {Ronald F.} and Laura Marsh and Brad Hiner and Neils, {Gregory D.} and Miguel Verbitsky and Sergey Kisselev and Elise Caccappolo and Ruth Ottman and Clark, {Lorraine N.}",
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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 - 2010/6/1

Y1 - 2010/6/1

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.

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