Parkinson disease phenotype in Ashkenazi jews with and without LRRK2 G2019S mutations

Roy N. Alcalay, Anat Mirelman, Rachel Saunders-Pullman, Ming X. Tang, Helen Mejia Santana, Deborah Raymond, Ernest Roos, Martha Orbe-Reilly, Tanya Gurevich, Anat Bar Shira, Mali Gana Weisz, Kira Yasinovsky, Maayan Zalis, Avner Thaler, Andres Deik, Matthew James Barrett, Jose Cabassa, Mark Groves, Ann L. Hunt, Naomi Lubarr & 29 others Marta San Luciano, Joan Miravite, Christina Palmese, Rivka Sachdev, Harini Sarva, Lawrence Severt, Vicki Shanker, Matthew Carrington Swan, Jeannie Soto-Valencia, Brooke Johannes, Robert Ortega, Stanley Fahn, Lucien Cote, Cheryl Waters, Pietro Mazzoni, Blair Ford, Elan Louis, Oren Levy, Llency Rosado, Diana Ruiz, Tsvyatko Dorovski, Michael Pauciulo, William Nichols, Avi Orr-Urtreger, Laurie Ozelius, Lorraine Clark, Nir Giladi, Susan Bressman, Karen S. Marder

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The phenotype of Parkinson's disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel-Aviv). Glucocerebrosidase (GBA) mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinson's Disease Rating Scale (UPDRS), the Geriatric Depression Scale (GDS) and the Non-Motor Symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. LRRK2 G2019S carriers (n=97) and non-carriers (n=391) were similar in age and age at onset of PD. Carriers had longer disease duration (8.6 years vs. 6.1 years; P5 years (P=0.042). Performance on the UPDRS, MoCA, GDS, and NMS did not differ by mutation status. PD in AJ LRRK2 G2019S mutation carriers is similar to idiopathic PD but is characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment.

Original languageEnglish (US)
Pages (from-to)1966-1971
Number of pages6
JournalMovement Disorders
Volume28
Issue number14
DOIs
StatePublished - Dec 2013
Externally publishedYes

Fingerprint

Jews
Leucine
Parkinson Disease
Phosphotransferases
Phenotype
Mutation
Glucosylceramidase
Depression
Geriatric Assessment
Geriatrics
Lower Extremity
Demography

Keywords

  • Genetics
  • LRRK2
  • Parkinson
  • Postural instability and gait difficulty

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Alcalay, R. N., Mirelman, A., Saunders-Pullman, R., Tang, M. X., Mejia Santana, H., Raymond, D., ... Marder, K. S. (2013). Parkinson disease phenotype in Ashkenazi jews with and without LRRK2 G2019S mutations. Movement Disorders, 28(14), 1966-1971. https://doi.org/10.1002/mds.25647

Parkinson disease phenotype in Ashkenazi jews with and without LRRK2 G2019S mutations. / Alcalay, Roy N.; Mirelman, Anat; Saunders-Pullman, Rachel; Tang, Ming X.; Mejia Santana, Helen; Raymond, Deborah; Roos, Ernest; Orbe-Reilly, Martha; Gurevich, Tanya; Bar Shira, Anat; Gana Weisz, Mali; Yasinovsky, Kira; Zalis, Maayan; Thaler, Avner; Deik, Andres; Barrett, Matthew James; Cabassa, Jose; Groves, Mark; Hunt, Ann L.; Lubarr, Naomi; San Luciano, Marta; Miravite, Joan; Palmese, Christina; Sachdev, Rivka; Sarva, Harini; Severt, Lawrence; Shanker, Vicki; Swan, Matthew Carrington; Soto-Valencia, Jeannie; Johannes, Brooke; Ortega, Robert; Fahn, Stanley; Cote, Lucien; Waters, Cheryl; Mazzoni, Pietro; Ford, Blair; Louis, Elan; Levy, Oren; Rosado, Llency; Ruiz, Diana; Dorovski, Tsvyatko; Pauciulo, Michael; Nichols, William; Orr-Urtreger, Avi; Ozelius, Laurie; Clark, Lorraine; Giladi, Nir; Bressman, Susan; Marder, Karen S.

In: Movement Disorders, Vol. 28, No. 14, 12.2013, p. 1966-1971.

Research output: Contribution to journalArticle

Alcalay, RN, Mirelman, A, Saunders-Pullman, R, Tang, MX, Mejia Santana, H, Raymond, D, Roos, E, Orbe-Reilly, M, Gurevich, T, Bar Shira, A, Gana Weisz, M, Yasinovsky, K, Zalis, M, Thaler, A, Deik, A, Barrett, MJ, Cabassa, J, Groves, M, Hunt, AL, Lubarr, N, San Luciano, M, Miravite, J, Palmese, C, Sachdev, R, Sarva, H, Severt, L, Shanker, V, Swan, MC, Soto-Valencia, J, Johannes, B, Ortega, R, Fahn, S, Cote, L, Waters, C, Mazzoni, P, Ford, B, Louis, E, Levy, O, Rosado, L, Ruiz, D, Dorovski, T, Pauciulo, M, Nichols, W, Orr-Urtreger, A, Ozelius, L, Clark, L, Giladi, N, Bressman, S & Marder, KS 2013, 'Parkinson disease phenotype in Ashkenazi jews with and without LRRK2 G2019S mutations', Movement Disorders, vol. 28, no. 14, pp. 1966-1971. https://doi.org/10.1002/mds.25647
Alcalay RN, Mirelman A, Saunders-Pullman R, Tang MX, Mejia Santana H, Raymond D et al. Parkinson disease phenotype in Ashkenazi jews with and without LRRK2 G2019S mutations. Movement Disorders. 2013 Dec;28(14):1966-1971. https://doi.org/10.1002/mds.25647
Alcalay, Roy N. ; Mirelman, Anat ; Saunders-Pullman, Rachel ; Tang, Ming X. ; Mejia Santana, Helen ; Raymond, Deborah ; Roos, Ernest ; Orbe-Reilly, Martha ; Gurevich, Tanya ; Bar Shira, Anat ; Gana Weisz, Mali ; Yasinovsky, Kira ; Zalis, Maayan ; Thaler, Avner ; Deik, Andres ; Barrett, Matthew James ; Cabassa, Jose ; Groves, Mark ; Hunt, Ann L. ; Lubarr, Naomi ; San Luciano, Marta ; Miravite, Joan ; Palmese, Christina ; Sachdev, Rivka ; Sarva, Harini ; Severt, Lawrence ; Shanker, Vicki ; Swan, Matthew Carrington ; Soto-Valencia, Jeannie ; Johannes, Brooke ; Ortega, Robert ; Fahn, Stanley ; Cote, Lucien ; Waters, Cheryl ; Mazzoni, Pietro ; Ford, Blair ; Louis, Elan ; Levy, Oren ; Rosado, Llency ; Ruiz, Diana ; Dorovski, Tsvyatko ; Pauciulo, Michael ; Nichols, William ; Orr-Urtreger, Avi ; Ozelius, Laurie ; Clark, Lorraine ; Giladi, Nir ; Bressman, Susan ; Marder, Karen S. / Parkinson disease phenotype in Ashkenazi jews with and without LRRK2 G2019S mutations. In: Movement Disorders. 2013 ; Vol. 28, No. 14. pp. 1966-1971.
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abstract = "The phenotype of Parkinson's disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel-Aviv). Glucocerebrosidase (GBA) mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinson's Disease Rating Scale (UPDRS), the Geriatric Depression Scale (GDS) and the Non-Motor Symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. LRRK2 G2019S carriers (n=97) and non-carriers (n=391) were similar in age and age at onset of PD. Carriers had longer disease duration (8.6 years vs. 6.1 years; P5 years (P=0.042). Performance on the UPDRS, MoCA, GDS, and NMS did not differ by mutation status. PD in AJ LRRK2 G2019S mutation carriers is similar to idiopathic PD but is characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment.",
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AU - Tang, Ming X.

AU - Mejia Santana, Helen

AU - Raymond, Deborah

AU - Roos, Ernest

AU - Orbe-Reilly, Martha

AU - Gurevich, Tanya

AU - Bar Shira, Anat

AU - Gana Weisz, Mali

AU - Yasinovsky, Kira

AU - Zalis, Maayan

AU - Thaler, Avner

AU - Deik, Andres

AU - Barrett, Matthew James

AU - Cabassa, Jose

AU - Groves, Mark

AU - Hunt, Ann L.

AU - Lubarr, Naomi

AU - San Luciano, Marta

AU - Miravite, Joan

AU - Palmese, Christina

AU - Sachdev, Rivka

AU - Sarva, Harini

AU - Severt, Lawrence

AU - Shanker, Vicki

AU - Swan, Matthew Carrington

AU - Soto-Valencia, Jeannie

AU - Johannes, Brooke

AU - Ortega, Robert

AU - Fahn, Stanley

AU - Cote, Lucien

AU - Waters, Cheryl

AU - Mazzoni, Pietro

AU - Ford, Blair

AU - Louis, Elan

AU - Levy, Oren

AU - Rosado, Llency

AU - Ruiz, Diana

AU - Dorovski, Tsvyatko

AU - Pauciulo, Michael

AU - Nichols, William

AU - Orr-Urtreger, Avi

AU - Ozelius, Laurie

AU - Clark, Lorraine

AU - Giladi, Nir

AU - Bressman, Susan

AU - Marder, Karen S.

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KW - Genetics

KW - LRRK2

KW - Parkinson

KW - Postural instability and gait difficulty

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