Skip to main content
AAN.com
Articles
February 4, 2015

Differential effects of severe vs mild GBA mutations on Parkinson disease

March 3, 2015 issue
84 (9) 880-887

Abstract

Objective:

To better define the genotype-phenotype correlations between the type of GBA (glucosidase, beta, acid) mutation, severe or mild, and the risk and age at onset (AAO), and potential mechanism of Parkinson disease (PD).

Methods:

We analyzed 1,000 patients of Ashkenazi-Jewish descent with PD for 7 founder GBA mutations, and conducted a meta-analysis of risk and AAO according to GBA genotype (severe or mild mutation). The meta-analysis included 11,453 patients with PD and 14,565 controls from worldwide populations. The statistical analysis was done with and without continuity correction (constant or empirical), considering biases that could potentially affect the results.

Results:

Among Ashkenazi-Jewish patients with PD, the odds ratios for PD were 2.2 and 10.3 for mild and severe GBA mutation carriers, respectively. The observed frequency of severe GBA mutation carriers among patients with PD was more than 4-fold than expected (4.4% vs 0.9%, respectively, p < 0.0001, Fisher exact test). In the different models of the meta-analysis, the odds ratios for PD ranged between 2.84 and 4.94 for mild GBA mutation carriers and 9.92 and 21.29 for severe GBA mutation carriers (p < 1 × 10−6 for all analyses). Pooled analysis demonstrated AAO of 53.1 (±11.2) and 58.1 (±10.6) years for severe and mild GBA mutation carriers, respectively (p = 4.3 × 10−5).

Conclusions:

These data demonstrate that mild and severe heterozygous GBA mutations differentially affect the risk and the AAO of PD. Our results have important implications for genetic counseling and clinical follow-up.

Get full access to this article

View all available purchase options and get full access to this article.

Supplementary Material

File (866.pdf)
File (figures.pdf)
File (table_e-1.pdf)

REFERENCES

1.
Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 2009;361:1651–1661.
2.
Choi JM, Kim WC, Lyoo CH, et al. Association of mutations in the glucocerebrosidase gene with Parkinson disease in a Korean population. Neurosci Lett 2012;514:12–15.
3.
Mitsui J, Mizuta I, Toyoda A, et al. Mutations for Gaucher disease confer high susceptibility to Parkinson disease. Arch Neurol 2009;66:571–576.
4.
Tan EK, Tong J, Fook-Chong S, et al. Glucocerebrosidase mutations and risk of Parkinson disease in Chinese patients. Arch Neurol 2007;64:1056–1058.
5.
Wu YR, Chen CM, Chao CY, et al. Glucocerebrosidase gene mutation is a risk factor for early onset of Parkinson disease among Taiwanese. J Neurol Neurosurg Psychiatry 2007;78:977–979.
6.
Ziegler SG, Eblan MJ, Gutti U, et al. Glucocerebrosidase mutations in Chinese subjects from Taiwan with sporadic Parkinson disease. Mol Genet Metab 2007;91:195–200.
7.
Bras J, Paisan-Ruiz C, Guerreiro R, et al. Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Portugal. Neurobiol Aging 2009;30:1515–1517.
8.
Emelyanov A, Boukina T, Yakimovskii A, et al. Glucocerebrosidase gene mutations are associated with Parkinson's disease in Russia. Mov Disord 2012;27:158–159.
9.
Kalinderi K, Bostantjopoulou S, Paisan-Ruiz C, Katsarou Z, Hardy J, Fidani L. Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece. Neurosci Lett 2009;452:87–89.
10.
Moraitou M, Hadjigeorgiou G, Monopolis I, et al. Beta-glucocerebrosidase gene mutations in two cohorts of Greek patients with sporadic Parkinson's disease. Mol Genet Metab 2011;104:149–152.
11.
Neumann J, Bras J, Deas E, et al. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease. Brain 2009;132:1783–1794.
12.
Seto-Salvia N, Pagonabarraga J, Houlden H, et al. Glucocerebrosidase mutations confer a greater risk of dementia during Parkinson's disease course. Mov Disord 2012;27:393–399.
13.
Lesage S, Condroyer C, Hecham N, et al. Mutations in the glucocerebrosidase gene confer a risk for Parkinson disease in North Africa. Neurology 2011;76:301–303.
14.
Clark LN, Ross BM, Wang Y, et al. Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease. Neurology 2007;69:1270–1277.
15.
Mata IF, Samii A, Schneer SH, et al. Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders. Arch Neurol 2008;65:379–382.
16.
Noreau A, Riviere JB, Diab S, et al. Glucocerebrosidase mutations in a French-Canadian Parkinson's disease cohort. Can J Neurol Sci 2011;38:772–773.
17.
Eblan MJ, Nguyen J, Ziegler SG, et al. Glucocerebrosidase mutations are also found in subjects with early-onset parkinsonism from Venezuela. Mov Disord 2006;21:282–283.
18.
Gonzalez-Del Rincon Mde L, Monroy Jaramillo N, Suarez Martinez AI, et al. The L444P GBA mutation is associated with early-onset Parkinson's disease in Mexican Mestizos. Clin Genet 2013;84:386–387.
19.
Guimaraes Bde C, Pereira AC, Rodrigues Fda C, et al. Glucocerebrosidase N370S and L444P mutations as risk factors for Parkinson's disease in Brazilian patients. Parkinsonism Relat Disord 2012;18:688–689.
20.
Spitz M, Rozenberg R, Pereira Lda V, Reis Barbosa E. Association between Parkinson's disease and glucocerebrosidase mutations in Brazil. Parkinsonism Relat Disord 2008;14:58–62.
21.
Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med 2004;351:1972–1977.
22.
Gan-Or Z, Giladi N, Rozovski U, et al. Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset. Neurology 2008;70:2277–2283.
23.
Beutler E, Gelbart T, Scott CR. Hematologically important mutations: Gaucher disease. Blood Cells Mol Dis 2005;35:355–364.
24.
Lesage S, Anheim M, Condroyer C, et al. Large-scale screening of the Gaucher's disease-related glucocerebrosidase gene in Europeans with Parkinson's disease. Hum Mol Genet 2011;20:202–210.
25.
Sidransky E, Lopez G. The link between the GBA gene and parkinsonism. Lancet Neurol 2012;11:986–998.
26.
Chabas A, Gort L, Diaz-Font A, et al. Perinatal lethal phenotype with generalized ichthyosis in a type 2 Gaucher disease patient with the [L444P;E326K]/P182L genotype: effect of the E326K change in neonatal and classic forms of the disease. Blood Cells Mol Dis 2005;35:253–258.
27.
Sunwoo MK, Kim SM, Lee S, Lee PH. Parkinsonism associated with glucocerebrosidase mutation. J Clin Neurol 2011;7:99–101.
28.
Lee JY, Lee BH, Kim GH, et al. Clinical and genetic characteristics of Gaucher disease according to phenotypic subgroups. Korean J Pediatr 2012;55:48–53.
29.
Kumar KR, Ramirez A, Gobel A, et al. Glucocerebrosidase mutations in a Serbian Parkinson's disease population. Eur J Neurol 2013;20:402–405.
30.
Alcalay RN, Caccappolo E, Mejia-Santana H, et al. Cognitive performance of GBA mutation carriers with early-onset PD: the CORE-PD Study. Neurology 2012;78:1434–1440.
31.
Giladi N, Mirelman A, Thaler A, Bar-Shira A, Gurevich T, Orr-Urtreger A. Fighting the risk of developing Parkinson's disease: clinical counseling for first degree relatives of patients with Parkinson's disease. J Neurol Sci 2011;310:17–20.
32.
Mazzulli JR, Xu YH, Sun Y, et al. Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 2011;146:37–52.
33.
Sato C, Morgan A, Lang AE, et al. Analysis of the glucocerebrosidase gene in Parkinson's disease. Mov Disord 2005;20:367–370.
34.
Toft M, Pielsticker L, Ross OA, Aasly JO, Farrer MJ. Glucocerebrosidase gene mutations and Parkinson disease in the Norwegian population. Neurology 2006;66:415–417.
35.
De Marco EV, Annesi G, Tarantino P, et al. Glucocerebrosidase gene mutations are associated with Parkinson's disease in southern Italy. Mov Disord 2008;23:460–463.
36.
Mao XY, Burgunder JM, Zhang ZJ, et al. Association between GBA L444P mutation and sporadic Parkinson's disease from mainland China. Neurosci Lett 2010;469:256–259.
37.
Sun QY, Guo JF, Wang L, et al. Glucocerebrosidase gene L444P mutation is a risk factor for Parkinson's disease in Chinese population. Mov Disord 2010;25:1005–1011.
38.
Huang CL, Wu-Chou YH, Lai SC, et al. Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson's disease in Taiwan. Eur J Neurol 2011;18:1227–1232.
39.
Wang Y, Liu L, Xiong J, et al. Glucocerebrosidase L444P mutation confers genetic risk for Parkinson's disease in central China. Behav Brain Funct 2012;8:57.
40.
Zhang X, Bao QQ, Zhuang XS, et al. Association of common variants in the glucocerebrosidase gene with high susceptibility to Parkinson's disease among Chinese. Chin J Physiol 2012;55:398–404.

Information & Authors

Information

Published In

Neurology®
Volume 84Number 9March 3, 2015
Pages: 880-887
PubMed: 25653295

Publication History

Received: August 11, 2014
Accepted: October 13, 2014
Published online: February 4, 2015
Published in print: March 3, 2015

Permissions

Request permissions for this article.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Study Funding

This work was supported by Tel Aviv Sourasky Medical Center Grant of Excellence, by the Kahn Foundation, by the Chief Scientist of the Israeli Ministry of Health (grant 3-4893), by the Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation (grant 1922/08), and by The Michael J. Fox Foundation for Parkinson's Research.

Authors

Affiliations & Disclosures

Ziv Gan-Or, MD, PhD*
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) Canadian Institute of Health Research, Post-doctoral fellowship, post-doctoral fellow, 2014-2016
Research Support, Academic Entities:
1.
(1) McGill University
Research Support, Foundations and Societies:
1.
(1) Michael J. Fox Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Idan Amshalom, BMedSci*
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Laura L. Kilarski, PhD
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Anat Bar-Shira, PhD
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Mali Gana-Weisz, PhD
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Anat Mirelman, PhD
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
MJFF foundation for Parkinson's research (AJ LRRK2 Study)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Karen Marder, MD
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Section editor, Current Neurology and Neuroscience
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NS036630(PI), 2UL1 RR024156-03(Director PCIR), 1U10NS077267-03 (CoPI),1R01NS073671-02(coI), 5R01N40068-10 (co-I),3U01AT000613-08 (coI) U01NS052592-05 (Co- I),5P20HG005535-02 (coI),5P50AG08702-24(coI), 5R01NS060113-03
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Parkinson Disease Foundation (investigator), Huntington's Disease Society of America (investigator), Parkinson Study Group (Co-chair, executive committee) Michael J Fox foundation, CHDI (investigator) CHDI
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Susan Bressman, MD
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
(1) Scientific Advisory Board of Bachmann Strauss Dystonia and Parkinsons's Foundation and (2) Michael J Fox Foundation for Parkinson's Research (3) Dystonia Medical Research Foundation
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Movement Disorders, Associate Editor, 2013-present
Patents:
1.
THAP1 gene testing
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH/NINDS RO1NS072515 NIH/NINDS Subrecipient PI 4/2011- 3/2015 NIH/NINDS P50NS037409-11 Consultant, 12/09-11/2014, NIH/NINDS KO2 NS073836, Mentor/Collaborator, 4/2011-3/2016 NIH/NINDS 1U10NS077308 Subrecipient Principal Investigator, 9/2011-8/2018
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Michael J Fox Foundation for Parkinson's Research
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Nir Giladi, MD
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
Serving on the Advisory Boards of UCB, Teva-Lundbeck, NeuroDerm, Intek Pharma. Chairing the Data Monitoring Safty Committee of Teva LTd.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Travel and speaking honeraria from Teva-Lundbeck, UCB, NeuroDerm, Schwartz Pharma, UCB, Merz
Editorial Boards:
1.
Associate Editor of the Journal of Neural Transmission and Current Treatment Opinion in Neurology On the Editorial Board of J Parkinson's disease
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Consultation fee to GSK, NeurDerm and Intek Pharma
Speakers' Bureaus:
1.
For Teva-Lundbeck and UCB
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Israel Science Foundation NIH, USA
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Michael J FOX, USA National Parkinson Foundation, USA
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Avi Orr-Urtreger, MD, PhD
From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George's, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) Israel Science Foundation Legacy Heritage Fund,No.1922/08, Co-P.I, 2008-2011 (2) Chief Scientist Department of Health Israel, No. 3? 4893, P.I, 2008-2011 (3) Tel Aviv Sourasky Medical Center
Research Support, Academic Entities:
1.
(3) ALS Association (USA) ALSA Grant ID 47717, Co-P.I, 2011-2014
Research Support, Foundations and Societies:
1.
(1)Kahn Foundation Israel P.I. (2)The Michael J. Fox Foundation for Parkinson?s Research Co-P.I and PI
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
Knock-Out Mice, Baylor Colledge of Medicine, Houston, Texas
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. Orr-Urtreger: [email protected] or Dr. Gan-Or: [email protected]
*
These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Ziv Gan-Or: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, accepts responsibility for conduct of research and will give final approval, acquisition of data, statistical analysis, study supervision. Idan Amshalom: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, accepts responsibility for conduct of research and will give final approval, statistical analysis. Laura L. Kilarski: analysis or interpretation of data, accepts responsibility for conduct of research and will give final approval. Anat Bar-Shira: drafting/revising the manuscript, accepts responsibility for conduct of research and will give final approval, acquisition of data. Mali Gana-Weisz: drafting/revising the manuscript, accepts responsibility for conduct of research and will give final approval, acquisition of data. Anat Mirelman: drafting/revising the manuscript, accepts responsibility for conduct of research and will give final approval, acquisition of data, study supervision. Karen Marder: drafting/revising the manuscript, accepts responsibility for conduct of research and will give final approval, acquisition of data. Susan Bressman: drafting/revising the manuscript, accepts responsibility for conduct of research and will give final approval, obtaining funding. Nir Giladi: drafting/revising the manuscript, accepts responsibility for conduct of research and will give final approval, obtaining funding. Avi Orr-Urtreger: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, accepts responsibility for conduct of research and will give final approval, study supervision, obtaining funding.

Metrics & Citations

Metrics

Citation information is sourced from Crossref Cited-by service.

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Preimplantation Genetic Testing (PGT) to Reduce the Risk for GBA-Related Parkinson’s Disease: Expanding the Applications for Embryo Selection, International Journal of Molecular Sciences, 26, 3, (912), (2025).https://doi.org/10.3390/ijms26030912
    Crossref
  2. Biological definitions of synucleinopathies should be anchored in clinical trajectories and encompass the complex biology of the disease, Journal of Parkinson’s Disease, (2025).https://doi.org/10.1177/1877718X241313443
    Crossref
  3. Biomarkers in Parkinson’s Disease, International Compendium of Movement Disorders, (221-237), (2025).https://doi.org/10.1017/9781108989855.021
    Crossref
  4. Exposure factors and clinical characteristics associated with Parkinson's disease in GBA1 variant carriers: A Chinese GBA1-PD intrafamilial survey, Parkinsonism & Related Disorders, 130, (107212), (2025).https://doi.org/10.1016/j.parkreldis.2024.107212
    Crossref
  5. GBA1 T369M and Parkinson's disease - Further evidence of a lack of association in the Swedish population, Parkinsonism & Related Disorders, 130, (107191), (2025).https://doi.org/10.1016/j.parkreldis.2024.107191
    Crossref
  6. Autophagic signatures in peripheral blood mononuclear cells from Parkinson's disease patients, Molecules and Cells, 48, 2, (100173), (2025).https://doi.org/10.1016/j.mocell.2024.100173
    Crossref
  7. The Genetics of Parkinson’s DiseaseParkinson Hastalığı Genetiği, Genel Tıp Dergisi, 34, 1, (136-143), (2024).https://doi.org/10.54005/geneltip.1337447
    Crossref
  8. GBA1-Associated Parkinson’s Disease Is a Distinct Entity, International Journal of Molecular Sciences, 25, 13, (7102), (2024).https://doi.org/10.3390/ijms25137102
    Crossref
  9. A Global Perspective of GBA1-Related Parkinson’s Disease: A Narrative Review, Genes, 15, 12, (1605), (2024).https://doi.org/10.3390/genes15121605
    Crossref
  10. The Genetic Landscape of Sleep Disorders in Parkinson’s Disease, Diagnostics, 14, 1, (106), (2024).https://doi.org/10.3390/diagnostics14010106
    Crossref
  11. See more
Loading...

View Options

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.

If you need immediate support or to place an order, please call or email customer service:

  • 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
  • 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
  • [email protected]

We appreciate your patience during this time and apologize for any inconvenience.

View options

PDF and All Supplements

Download PDF and Supplementary Material

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Figures

Tables

Media

Share

Share

Share article link

Share