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Article Dans Une Revue Neurology Année : 2021

Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder

Kheireddin Mufti (1) , Eric Yu (2) , Uladzislau Rudakou (2) , Lynne Krohn (3) , Jennifer A Ruskey (4) , Farnaz Asayesh (4) , Sandra B Laurent (2) , Dan Spiegelman (4) , Isabelle Arnulf (5) , Jacques y Montplaisir (6) , Jean-François Gagnon (7) , Alex Desautels (7) , Yves Dauvilliers (5) , Gian Luigi Gigli (8) , Mariarosaria Valente (8) , Francesco Janes (8) , Andrea Bernardini (9) , Birgit Högl (10) , Ambra Stefani (10) , Evi Holzknecht (10) , Karel Sonka (11) , David Kemlink (12) , Wolfgang Oertel (13) , Annette Janzen (13) , Giuseppe Plazzi (14) , Elena Antelmi (14) , Michela Figorilli (15) , Monica Puligheddu (15) , Brit Mollenhauer (16) , Claudia Trenkwalder (16) , Friederike Sixel-Döring (17) , Valérie Cochen de Cock (18, 19) , Christelle Charley Monaca (20) , Anna Heidbreder (21) , Luigi Ferini-Strambi (22) , Femke Dijkstra (23) , Mineke Viaene (23) , Beatriz Abril (24) , Bradley F Boeve (25) , Jean-François Trempe (3) , Guy A Rouleau (26) , Ronald B Postuma (27) , Ziv Gan-Or (28)
1 ICM - Institut du Cerveau = Paris Brain Institute
2 Montreal Neurological Institute and Hospital
3 McGill University = Université McGill [Montréal, Canada]
4 Department of Neurology and Neurosurgery [Montreal]
5 CHU Pitié-Salpêtrière [AP-HP]
6 UQAM - Université du Québec à Montréal = University of Québec in Montréal
7 CEAMS - Centre d'études avancées en Médecine du Sommeil
8 Università degli Studi di Udine - University of Udine [Italie]
9 UNIMI - Università degli Studi di Milano = University of Milan
10 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
11 Medicine Charles University and General Faculty Hospital in Prague
12 1. LF UK / 1st Faculty of Medicine - 1. lékařská fakulta, Univerzita Karlova [Praha, Česká republika] = First Faculty of Medicine, Charles University [Prague, Czech Republic]
13 Philipps Universität Marburg = Philipps University of Marburg
14 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
15 UniCa - Università degli Studi di Cagliari = University of Cagliari
16 Georg-August-University = Georg-August-Universität Göttingen
17 Paracelsus-Elena-Klinik, Kassel, Germany.
18 CHU Saint-Antoine [AP-HP]
19 Euromov DHM - EuroMov - Digital Health in Motion
20 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
21 UKM - University Hospital Münster - Universitaetsklinikum Muenster [Germany]
22 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
23 Jessa Ziekenhuis [Hasselt]
24 UGR - Universidad de Granada = University of Granada
25 Mayo Clinic
26 CHU Sainte Justine [Montréal]
27 Montreal General Hospital
28 NIH - National Institutes of Health [Bethesda, MD, USA]
Kheireddin Mufti
  • Fonction : Auteur
Institut du Cerveau = Paris Brain Institute
Eric Yu
  • Fonction : Auteur
Montreal Neurological Institute and Hospital
Uladzislau Rudakou
Montreal Neurological Institute and Hospital
Lynne Krohn
McGill University = Université McGill [Montréal, Canada]
Jennifer A Ruskey
  • Fonction : Auteur
Department of Neurology and Neurosurgery [Montreal]
Farnaz Asayesh
  • Fonction : Auteur
Department of Neurology and Neurosurgery [Montreal]
Sandra B Laurent
  • Fonction : Auteur
Montreal Neurological Institute and Hospital
Dan Spiegelman
  • Fonction : Auteur
Department of Neurology and Neurosurgery [Montreal]
Isabelle Arnulf
CHU Pitié-Salpêtrière [AP-HP]
Jacques y Montplaisir
  • Fonction : Auteur
Université du Québec à Montréal = University of Québec in Montréal
Jean-François Gagnon
  • Fonction : Auteur
Centre d'études avancées en Médecine du Sommeil
Alex Desautels
Centre d'études avancées en Médecine du Sommeil
Yves Dauvilliers
CHU Pitié-Salpêtrière [AP-HP]
Gian Luigi Gigli
  • Fonction : Auteur
Università degli Studi di Udine - University of Udine [Italie]
Mariarosaria Valente
Università degli Studi di Udine - University of Udine [Italie]
Francesco Janes
  • Fonction : Auteur
Università degli Studi di Udine - University of Udine [Italie]
Andrea Bernardini
  • Fonction : Auteur
Università degli Studi di Milano = University of Milan
Birgit Högl
  • Fonction : Auteur
Innsbruck Medical University = Medizinische Universität Innsbruck
Ambra Stefani
Innsbruck Medical University = Medizinische Universität Innsbruck
Evi Holzknecht
  • Fonction : Auteur
Innsbruck Medical University = Medizinische Universität Innsbruck
Karel Sonka
Medicine Charles University and General Faculty Hospital in Prague
David Kemlink
1. lékařská fakulta, Univerzita Karlova [Praha, Česká republika] = First Faculty of Medicine, Charles University [Prague, Czech Republic]
Wolfgang Oertel
  • Fonction : Auteur
Philipps Universität Marburg = Philipps University of Marburg
Annette Janzen
  • Fonction : Auteur
Philipps Universität Marburg = Philipps University of Marburg
Giuseppe Plazzi
Alma Mater Studiorum Università di Bologna = University of Bologna
Elena Antelmi
Alma Mater Studiorum Università di Bologna = University of Bologna
Michela Figorilli
Università degli Studi di Cagliari = University of Cagliari
Monica Puligheddu
Università degli Studi di Cagliari = University of Cagliari
Brit Mollenhauer
Georg-August-University = Georg-August-Universität Göttingen
Claudia Trenkwalder
  • Fonction : Auteur
Georg-August-University = Georg-August-Universität Göttingen
Friederike Sixel-Döring
  • Fonction : Auteur
Paracelsus-Elena-Klinik, Kassel, Germany.
Valérie Cochen de Cock
CHU Saint-Antoine [AP-HP]
EuroMov - Digital Health in Motion
Christelle Charley Monaca
  • Fonction : Auteur
Centre Hospitalier Régional Universitaire [CHU Lille]
Anna Heidbreder
University Hospital Münster - Universitaetsklinikum Muenster [Germany]
Luigi Ferini-Strambi
Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
Femke Dijkstra
Jessa Ziekenhuis [Hasselt]
Mineke Viaene
Jessa Ziekenhuis [Hasselt]
Beatriz Abril
  • Fonction : Auteur
Universidad de Granada = University of Granada
Bradley F Boeve
  • Fonction : Auteur
Mayo Clinic
Jean-François Trempe
  • Fonction : Auteur
McGill University = Université McGill [Montréal, Canada]
Guy A Rouleau
CHU Sainte Justine [Montréal]
Ronald B Postuma
  • Fonction : Auteur
Montreal General Hospital
Ziv Gan-Or
  • Fonction : Auteur
  • PersonId : 1102060
National Institutes of Health [Bethesda, MD, USA]

Résumé

Objective To examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated REM sleep behavior disorder (iRBD). Methods We fully sequenced 25 genes previously identified in GWASs of PD in a total of 1,039 patients with iRBD and 1,852 controls. The role of rare heterozygous variants in these genes was examined with burden tests. The contribution of biallelic variants was further tested. To examine the potential effect of rare nonsynonymous BST1 variants on the protein structure, we performed in silico structural analysis. Finally, we examined the association of common variants using logistic regression adjusted for age and sex. Results We found an association between rare heterozygous nonsynonymous variants in BST1 and iRBD (p = 0.0003 at coverage >50× and 0.0004 at >30×), driven mainly by 3 nonsynonymous variants (p.V85M, p.I101V, and p.V272M) found in 22 (1.2%) controls vs 2 (0.2%) patients. All 3 variants seem to be loss-of-function variants with a potential effect on the protein structure and stability. Rare noncoding heterozygous variants in LAMP3 were also associated with iRBD (p = 0.0006 at >30×). We found no association between rare heterozygous variants in the rest of genes and iRBD. Several carriers of biallelic variants were identified, yet there was no overrepresentation in iRBD. Conclusion Our results suggest that rare coding variants in BST1 and rare noncoding variants in LAMP3 are associated with iRBD. Additional studies are required to replicate these results and to examine whether loss of function of BST1 could be a therapeutic target.

Domaines

Neurosciences [q-bio.NC]
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https://hal.sorbonne-universite.fr/hal-03260134

Soumis le : lundi 14 juin 2021-16:53:30

Dernière modification le : samedi 20 avril 2024-03:20:56

Archivage à long terme le : jeudi 16 septembre 2021-08:24:05

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hal-03260134 , version 1 (14-06-2021)

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Kheireddin Mufti, Eric Yu, Uladzislau Rudakou, Lynne Krohn, Jennifer A Ruskey, et al.. Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder. Neurology, 2021, 96 (10), pp.e1402 - e1412. ⟨10.1212/wnl.0000000000011464⟩. ⟨hal-03260134⟩

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