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 FahnLucien 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 journalArticlepeer-review

101 Scopus citations


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 (US)
Pages (from-to)1116-1122
Number of pages7
JournalArchives of neurology
Issue number9
StatePublished - Sep 2010
Externally publishedYes

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology


Dive into the research topics of 'Frequency of known mutations in early-onset Parkinson disease: Implication for genetic counseling: The consortium on risk for early onset Parkinson disease study'. Together they form a unique fingerprint.

Cite this