Frequency of known mutations in early-onset Parkinson disease

Implication for genetic counseling: The consortium on risk for early onset Parkinson disease study

Roy N. Alcalay, Elise Caccappolo, Helen Mejia-Santana, Ming Xin Tang, Llency Rosado, Barbara M. Ross, Miguel Verbitsky, Sergey Kisselev, Elan D. Louis, Cynthia Comella, Amy Colcher, Danna Jennings, Martha A. Nance, Susan B. Bressman, William K Scott, Caroline Tanner, Susan Mickel, Howard Andrews, Cheryl Waters, Stanley Fahn & 13 others Lucien Cote, Steven Frucht, Blair Ford, Michael Rezak, Kevin Novak, Joseph H. Friedman, Ronald Pfeiffer, Laura Marsh, Bradley Hiner, Andrew Siderowf, Ruth Ottman, Karen Marder, Lorraine N. Clark

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Objective: To assess the frequency and clinical characteristics of carriers of previously identified mutations in 6 genes associated with early-onset Parkinson disease (PD) and provide empirical data that can be used to inform genetic counseling. Design: Cross-sectional observational study. Setting: Thirteen movement disorders centers. Patients: Nine hundred fifty-three individuals with early-onset PD defined as age at onset (AAO) younger than 51 years. Participants included 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Intervention: Mutations in SNCA, PRKN, PINK1, DJ1, LRRK2, and GBA were assessed. A validated family history interview and the Unified Parkinson Disease Rating Scale were administered. Demographic and phenotypic characteristics were compared among groups defined by mutation status. Main Outcome Measure: Mutation carrier frequency stratified by AAO and ethnic background. Results: One hundred fifty-eight (16.6%) participants had mutations, including 64 (6.7%) PRKN, 35 (3.6%) LRRK2 G2019S, 64 (6.7%) GBA, and 1 (0.2%) DJ1. Mutation carriers were more frequent in those with an AAO of 30 years or younger compared with those with AAO between 31 and 50 years (40.6% vs 14.6%, P<.001), in individuals who reported Jewish ancestry (32.4% vs 13.7%, P<.001), and in those reporting a first-degree family history of PD(23.9% vs 15.1%, P=.01). Hispanic individuals were more likely to be PRKN carriers than non-Hispanic individuals (15.6% vs 5.9%, P=.003). The GBA L444P mutation was associated with a higher mean Unified Parkinson Disease Rating Scale III score after adjustment for covariates. Conclusion: Individuals of Jewish or Hispanic ancestry with early-onset PD, those with AAO of 30 years or younger, and those with a history of PD in a first-degree relative may benefit from genetic counseling.

Original languageEnglish
Pages (from-to)1116-1122
Number of pages7
JournalArchives of Neurology
Volume67
Issue number9
DOIs
StatePublished - Sep 1 2010

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Genetic Counseling
Mutation Rate
Parkinson Disease
Age of Onset
Mutation
Hispanic Americans
Movement Disorders
Parkinson's Disease
Onset
Observational Studies
Cross-Sectional Studies
Demography
Outcome Assessment (Health Care)
Interviews
Carrier
Genes

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

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

In: Archives of Neurology, Vol. 67, No. 9, 01.09.2010, p. 1116-1122.

Research output: Contribution to journalArticle

Alcalay, RN, Caccappolo, E, Mejia-Santana, H, Tang, MX, Rosado, L, Ross, BM, Verbitsky, M, Kisselev, S, Louis, ED, Comella, C, Colcher, A, Jennings, D, Nance, MA, Bressman, SB, Scott, WK, Tanner, C, Mickel, S, Andrews, H, Waters, C, Fahn, S, Cote, L, Frucht, S, Ford, B, Rezak, M, Novak, K, Friedman, JH, Pfeiffer, R, Marsh, L, Hiner, B, Siderowf, A, Ottman, R, Marder, K & Clark, LN 2010, 'Frequency of known mutations in early-onset Parkinson disease: Implication for genetic counseling: The consortium on risk for early onset Parkinson disease study', Archives of Neurology, vol. 67, no. 9, pp. 1116-1122. https://doi.org/10.1001/archneurol.2010.194
Alcalay, Roy N. ; Caccappolo, Elise ; Mejia-Santana, Helen ; Tang, Ming Xin ; Rosado, Llency ; Ross, Barbara M. ; Verbitsky, Miguel ; Kisselev, Sergey ; Louis, Elan D. ; Comella, Cynthia ; Colcher, Amy ; Jennings, Danna ; Nance, Martha A. ; Bressman, Susan B. ; Scott, William K ; Tanner, Caroline ; Mickel, Susan ; Andrews, Howard ; Waters, Cheryl ; Fahn, Stanley ; Cote, Lucien ; Frucht, Steven ; Ford, Blair ; Rezak, Michael ; Novak, Kevin ; Friedman, Joseph H. ; Pfeiffer, Ronald ; Marsh, Laura ; Hiner, Bradley ; Siderowf, Andrew ; Ottman, Ruth ; Marder, Karen ; Clark, Lorraine N. / Frequency of known mutations in early-onset Parkinson disease : Implication for genetic counseling: The consortium on risk for early onset Parkinson disease study. In: Archives of Neurology. 2010 ; Vol. 67, No. 9. pp. 1116-1122.
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abstract = "Objective: To assess the frequency and clinical characteristics of carriers of previously identified mutations in 6 genes associated with early-onset Parkinson disease (PD) and provide empirical data that can be used to inform genetic counseling. Design: Cross-sectional observational study. Setting: Thirteen movement disorders centers. Patients: Nine hundred fifty-three individuals with early-onset PD defined as age at onset (AAO) younger than 51 years. Participants included 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Intervention: Mutations in SNCA, PRKN, PINK1, DJ1, LRRK2, and GBA were assessed. A validated family history interview and the Unified Parkinson Disease Rating Scale were administered. Demographic and phenotypic characteristics were compared among groups defined by mutation status. Main Outcome Measure: Mutation carrier frequency stratified by AAO and ethnic background. Results: One hundred fifty-eight (16.6{\%}) participants had mutations, including 64 (6.7{\%}) PRKN, 35 (3.6{\%}) LRRK2 G2019S, 64 (6.7{\%}) GBA, and 1 (0.2{\%}) DJ1. Mutation carriers were more frequent in those with an AAO of 30 years or younger compared with those with AAO between 31 and 50 years (40.6{\%} vs 14.6{\%}, P<.001), in individuals who reported Jewish ancestry (32.4{\%} vs 13.7{\%}, P<.001), and in those reporting a first-degree family history of PD(23.9{\%} vs 15.1{\%}, P=.01). Hispanic individuals were more likely to be PRKN carriers than non-Hispanic individuals (15.6{\%} vs 5.9{\%}, P=.003). The GBA L444P mutation was associated with a higher mean Unified Parkinson Disease Rating Scale III score after adjustment for covariates. Conclusion: Individuals of Jewish or Hispanic ancestry with early-onset PD, those with AAO of 30 years or younger, and those with a history of PD in a first-degree relative may benefit from genetic counseling.",
author = "Alcalay, {Roy N.} and Elise Caccappolo and Helen Mejia-Santana and Tang, {Ming Xin} and Llency Rosado and Ross, {Barbara M.} and Miguel Verbitsky and Sergey Kisselev and Louis, {Elan D.} and Cynthia Comella and Amy Colcher and Danna Jennings and Nance, {Martha A.} and Bressman, {Susan B.} and Scott, {William K} and Caroline Tanner and Susan Mickel and Howard Andrews and Cheryl Waters and Stanley Fahn and Lucien Cote and Steven Frucht and Blair Ford and Michael Rezak and Kevin Novak and Friedman, {Joseph H.} and Ronald Pfeiffer and Laura Marsh and Bradley Hiner and Andrew Siderowf and Ruth Ottman and Karen Marder and Clark, {Lorraine N.}",
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T1 - Frequency of known mutations in early-onset Parkinson disease

T2 - Implication for genetic counseling: The consortium on risk for early onset Parkinson disease study

AU - Alcalay, Roy N.

AU - Caccappolo, Elise

AU - Mejia-Santana, Helen

AU - Tang, Ming Xin

AU - Rosado, Llency

AU - Ross, Barbara M.

AU - Verbitsky, Miguel

AU - Kisselev, Sergey

AU - Louis, Elan D.

AU - Comella, Cynthia

AU - Colcher, Amy

AU - Jennings, Danna

AU - Nance, Martha A.

AU - Bressman, Susan B.

AU - Scott, William K

AU - Tanner, Caroline

AU - Mickel, Susan

AU - Andrews, Howard

AU - Waters, Cheryl

AU - Fahn, Stanley

AU - Cote, Lucien

AU - Frucht, Steven

AU - Ford, Blair

AU - Rezak, Michael

AU - Novak, Kevin

AU - Friedman, Joseph H.

AU - Pfeiffer, Ronald

AU - Marsh, Laura

AU - Hiner, Bradley

AU - Siderowf, Andrew

AU - Ottman, Ruth

AU - Marder, Karen

AU - Clark, Lorraine N.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Objective: To assess the frequency and clinical characteristics of carriers of previously identified mutations in 6 genes associated with early-onset Parkinson disease (PD) and provide empirical data that can be used to inform genetic counseling. Design: Cross-sectional observational study. Setting: Thirteen movement disorders centers. Patients: Nine hundred fifty-three individuals with early-onset PD defined as age at onset (AAO) younger than 51 years. Participants included 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Intervention: Mutations in SNCA, PRKN, PINK1, DJ1, LRRK2, and GBA were assessed. A validated family history interview and the Unified Parkinson Disease Rating Scale were administered. Demographic and phenotypic characteristics were compared among groups defined by mutation status. Main Outcome Measure: Mutation carrier frequency stratified by AAO and ethnic background. Results: One hundred fifty-eight (16.6%) participants had mutations, including 64 (6.7%) PRKN, 35 (3.6%) LRRK2 G2019S, 64 (6.7%) GBA, and 1 (0.2%) DJ1. Mutation carriers were more frequent in those with an AAO of 30 years or younger compared with those with AAO between 31 and 50 years (40.6% vs 14.6%, P<.001), in individuals who reported Jewish ancestry (32.4% vs 13.7%, P<.001), and in those reporting a first-degree family history of PD(23.9% vs 15.1%, P=.01). Hispanic individuals were more likely to be PRKN carriers than non-Hispanic individuals (15.6% vs 5.9%, P=.003). The GBA L444P mutation was associated with a higher mean Unified Parkinson Disease Rating Scale III score after adjustment for covariates. Conclusion: Individuals of Jewish or Hispanic ancestry with early-onset PD, those with AAO of 30 years or younger, and those with a history of PD in a first-degree relative may benefit from genetic counseling.

AB - Objective: To assess the frequency and clinical characteristics of carriers of previously identified mutations in 6 genes associated with early-onset Parkinson disease (PD) and provide empirical data that can be used to inform genetic counseling. Design: Cross-sectional observational study. Setting: Thirteen movement disorders centers. Patients: Nine hundred fifty-three individuals with early-onset PD defined as age at onset (AAO) younger than 51 years. Participants included 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Intervention: Mutations in SNCA, PRKN, PINK1, DJ1, LRRK2, and GBA were assessed. A validated family history interview and the Unified Parkinson Disease Rating Scale were administered. Demographic and phenotypic characteristics were compared among groups defined by mutation status. Main Outcome Measure: Mutation carrier frequency stratified by AAO and ethnic background. Results: One hundred fifty-eight (16.6%) participants had mutations, including 64 (6.7%) PRKN, 35 (3.6%) LRRK2 G2019S, 64 (6.7%) GBA, and 1 (0.2%) DJ1. Mutation carriers were more frequent in those with an AAO of 30 years or younger compared with those with AAO between 31 and 50 years (40.6% vs 14.6%, P<.001), in individuals who reported Jewish ancestry (32.4% vs 13.7%, P<.001), and in those reporting a first-degree family history of PD(23.9% vs 15.1%, P=.01). Hispanic individuals were more likely to be PRKN carriers than non-Hispanic individuals (15.6% vs 5.9%, P=.003). The GBA L444P mutation was associated with a higher mean Unified Parkinson Disease Rating Scale III score after adjustment for covariates. Conclusion: Individuals of Jewish or Hispanic ancestry with early-onset PD, those with AAO of 30 years or younger, and those with a history of PD in a first-degree relative may benefit from genetic counseling.

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