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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, [......],
Michael Rezak,
Kevin Novak,
Joseph H Friedman,
Ronald Pfeiffer,
Laura Marsh, Bradley Hiner,
Andrew Siderowf,
Ruth Ottman,
Karen Marder,
Lorraine N Clark
[show abstract]
[hide abstract]
ABSTRACT: 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.
Cross-sectional observational study.
Thirteen movement disorders centers.
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.
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.
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.
Archives of neurology 09/2010; 67(9):1116-22. · 6.31 Impact Factor
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Roy N Alcalay,
Helen Mejia-Santana,
Ming X Tang,
Brian Rakitin,
Llency Rosado,
Barbara Ross,
Miguel Verbitsky,
Sergey Kisselev,
Elan D Louis,
Cynthia L Comella, [......],
Kevin Novak,
Joseph H Friedman,
Ronald Pfeiffer,
Laura Marsh, Bradley Hiner,
Andrew Siderowf,
Ruth Ottman,
Lorraine N Clark,
Karen S Marder,
Elise Caccappolo
[show abstract]
[hide abstract]
ABSTRACT: While little is known about risk factors for cognitive impairment in early onset Parkinson disease (EOPD), postmortem studies have shown an association between dementia with Lewy bodies (DLB) and glucocerebrosidase (GBA) mutation. We compared Mini-Mental State Examination (MMSE) performance and self-reported cognitive impairment in 699 EOPD participants genotyped for mutations in parkin (PRKN), leucine-rich repeat kinase-2 (LRRK2), and GBA. Logistic regression was used to assess the association between reported cognitive impairment and MMSE score, as well as between GBA group membership and self-reported impairment and MMSE. GBA carriers reported more impairment, but MMSE performance did not differ among genetic groups. Detailed neuropsychological testing is required to explore the association between cognitive impairment and GBA mutations.
Journal of Clinical and Experimental Neuropsychology 02/2010; 32(7):775-9. · 2.13 Impact Factor
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Roy N Alcalay,
Helen Mejia-Santana,
Ming Xin Tang,
Llency Rosado,
Miguel Verbitsky,
Sergey Kisselev,
Barbara M Ross,
Elan D Louis,
Cynthia L Comella,
Amy Colcher, [......],
Kevin Novak,
Joseph H Friedman,
Ronald Pfeiffer,
Laura Marsh, Bradley Hiner,
Andrew Siderowf,
Elise Caccappolo,
Ruth Ottman,
Lorraine N Clark,
Karen S Marder
[show abstract]
[hide abstract]
ABSTRACT: To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype.
Cross-sectional observational study.
Thirteen movement disorders centers.
Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years.
LRRK2 mutation status and Parkinson disease motor phenotype: tremor dominant or PIGD. Demographic information, family history of Parkinson disease, and the Unified Parkinson's Disease Rating Scale score were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C, and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish ancestry, levodopa dose, and family history of Parkinson disease.
Thirty-four cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be Ashkenazi Jewish (55.9% vs 11.9%; P < .001) but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (P = .03) and were more likely to have a PIGD phenotype (92.3% vs 58.9%; P = .003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and Ashkenazi Jewish ancestry (odds ratio, 17.7; P < .001).
Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course.
Archives of neurology 12/2009; 66(12):1517-22. · 6.31 Impact Factor
