GBA variants in REM sleep behavior disorder: A multicenter study.
Lynne Krohn
(1)
,
Jennifer A. Ruskey
(2)
,
Uladzislau Rudakou
(2)
,
Etienne Leveille
(3, 2)
,
Farnaz Asayesh
(4)
,
Michele T.M. Hu
(2)
,
Isabelle Arnulf
(5)
,
Yves Dauvilliers
(6, 7)
,
Birgitte Högl
(8)
,
Ambra Stefani
(8)
,
Christelle Charley-Monaca
(9, 10)
,
Beatriz Abril
(11)
,
Giuseppe Plazzi
(12)
,
Elena Antelmi
(12)
,
Luigi Ferini-Strambi
(13)
,
Anna Heidbreder
(14)
,
Bradley F. Boeve
(15)
,
Alberto J. Espay
(16)
,
Valerie Cochen de Cock
(17)
,
Brit Mollenhauer
(18)
,
Friederike Sixel-Döring
(19)
,
Claudia Trenkwalder
(18)
,
Karel Sonka
(20)
,
David Kemlink
(21)
,
Michela Figorilli
(22)
,
Monica Puligheddu
(22)
,
Femke Dijkstra
,
Mineke Viaene
,
Wolfgang Oertel
(19)
,
Marco Toffoli
(23)
,
Gian Luigi Gigli
(23)
,
Mariarosaria Valente
(23)
,
Jean-François Gagnon
(24)
,
Alex Desautels
(25)
,
Jacques Montplaisir
(26)
,
Ronald B. Postuma
(26)
,
Guy A Rouleau
(1)
,
Ziv Gan-Or
(27)
1
McGill University = Université McGill [Montréal, Canada]
2 MUHC - McGill University Health Center [Montreal]
3 3IT - Institut Interdisciplinaire d'Innovation Technologique [Sherbrooke]
4 Department of Neurology and Neurosurgery [Montreal]
5 CHU Pitié-Salpêtrière [AP-HP]
6 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
7 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
8 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
9 TCDV - Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046
10 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
11 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
12 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
13 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
14 UKM - University Hospital Münster - Universitaetsklinikum Muenster [Germany]
15 Mayo Clinic [Rochester]
16 UC - University of Cincinnati
17 EuroMov - Euromov
18 UMG - University Medical Center Göttingen
19 Philipps Universität Marburg = Philipps University of Marburg
20 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
21 1. LF UK / 1st Faculty of Medicine - 1. lékařská fakulta, Univerzita Karlova [Praha, Česká republika] = First Faculty of Medicine, Charles University [Prague, Czech Republic]
22 University of Cagliari
23 Università degli Studi di Udine - University of Udine [Italie]
24 University of Alberta
25 UdeM - Université de Montréal
26 Hôpital du Sacré-Coeur de Montréal
27 NIH - National Institutes of Health [Bethesda, MD, USA]
2 MUHC - McGill University Health Center [Montreal]
3 3IT - Institut Interdisciplinaire d'Innovation Technologique [Sherbrooke]
4 Department of Neurology and Neurosurgery [Montreal]
5 CHU Pitié-Salpêtrière [AP-HP]
6 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
7 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
8 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
9 TCDV - Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046
10 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
11 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
12 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
13 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
14 UKM - University Hospital Münster - Universitaetsklinikum Muenster [Germany]
15 Mayo Clinic [Rochester]
16 UC - University of Cincinnati
17 EuroMov - Euromov
18 UMG - University Medical Center Göttingen
19 Philipps Universität Marburg = Philipps University of Marburg
20 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
21 1. LF UK / 1st Faculty of Medicine - 1. lékařská fakulta, Univerzita Karlova [Praha, Česká republika] = First Faculty of Medicine, Charles University [Prague, Czech Republic]
22 University of Cagliari
23 Università degli Studi di Udine - University of Udine [Italie]
24 University of Alberta
25 UdeM - Université de Montréal
26 Hôpital du Sacré-Coeur de Montréal
27 NIH - National Institutes of Health [Bethesda, MD, USA]
Lynne Krohn
- Fonction : Auteur
- PersonId : 800396
- ORCID : 0000-0001-6554-1666
Uladzislau Rudakou
- Fonction : Auteur
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Michele T.M. Hu
- Fonction : Auteur
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Yves Dauvilliers
- Fonction : Auteur
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Ambra Stefani
- Fonction : Auteur
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- ORCID : 0000-0003-4259-8824
Giuseppe Plazzi
- Fonction : Auteur
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- ORCID : 0000-0001-6937-3065
Elena Antelmi
- Fonction : Auteur
- PersonId : 791033
- ORCID : 0000-0003-1739-6139
Luigi Ferini-Strambi
- Fonction : Auteur
- PersonId : 791696
- ORCID : 0000-0003-2867-5424
Anna Heidbreder
- Fonction : Auteur
- PersonId : 791697
- ORCID : 0000-0002-9552-7619
Brit Mollenhauer
- Fonction : Auteur
- PersonId : 792182
- ORCID : 0000-0001-8437-3645
Karel Sonka
- Fonction : Auteur
- PersonId : 763639
- ORCID : 0000-0001-5773-9656
David Kemlink
- Fonction : Auteur
- PersonId : 763638
- ORCID : 0000-0003-1398-5796
Michela Figorilli
- Fonction : Auteur
- PersonId : 785857
- ORCID : 0000-0002-1638-1384
Monica Puligheddu
- Fonction : Auteur
- PersonId : 785858
- ORCID : 0000-0002-6837-6608
Femke Dijkstra
- Fonction : Auteur
- PersonId : 807692
- ORCID : 0000-0002-8621-977X
Mineke Viaene
- Fonction : Auteur
- PersonId : 807693
- ORCID : 0000-0003-3702-106X
Wolfgang Oertel
- Fonction : Auteur
- PersonId : 956206
Marco Toffoli
- Fonction : Auteur
- PersonId : 818379
- ORCID : 0000-0002-3255-9648
Gian Luigi Gigli
- Fonction : Auteur
- PersonId : 818380
- ORCID : 0000-0003-3526-1414
Mariarosaria Valente
- Fonction : Auteur
- PersonId : 807690
- ORCID : 0000-0001-6077-1315
Alex Desautels
- Fonction : Auteur
- PersonId : 791699
- ORCID : 0000-0002-2495-5675
Guy A Rouleau
- Fonction : Auteur
- PersonId : 889825
Résumé
Objective: To study the role of GBA variants in the risk for isolated REM sleep behavior disorder (iRBD) and conversion to overt neurodegeneration.Methods: A total of 4,147 individuals were included: 1,061 patients with iRBD and 3,086 controls. GBA was fully sequenced using molecular inversion probes and Sanger sequencing. We analyzed the effects of GBA variants on the risk of iRBD, age at onset (AAO), and conversion rates.Results: GBA variants were found in 9.5% of patients with iRBD compared to 4.1% of controls (odds ratio, 2.45; 95% confidence interval [CI], 1.87-3.22; p = 1 × 10-10). The estimated OR for mild p.N370S variant carriers was 3.69 (95% CI, 1.90-7.14; p = 3.5 × 10-5), while for severe variant carriers it was 17.55 (95% CI, 2.11-145.9; p = 0.0015). Carriers of severe GBA variants had an average AAO of 52.8 years, 7-8 years earlier than those with mild variants or noncarriers (p = 0.029). Of the GBA variant carriers with available data, 52.5% had converted, compared to 35.6% of noncarriers (p = 0.011), with a trend for faster conversion among severe GBA variant carriers. However, the results on AAO and conversion were based on small numbers and should be interpreted with caution.Conclusions: GBA variants robustly and differentially increase the risk of iRBD. The rate of conversion to neurodegeneration is also increased and may be faster among severe GBA variant carriers, although confirmation will be required in larger samples. Screening for RBD in healthy carriers of GBA variants should be studied as a potential way to identify GBA variant carriers who will develop a synucleinopathy in the future.
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