Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder - Sorbonne Université Access content directly
Journal Articles Neurology Year : 2021

Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder

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 Service de Pathologies du sommeil [CHU Pitié-Salpêtrière]
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 Università degli Studi di Milano, IRCCS Policlinico San Donato
10 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
11 Medicine Charles University and General Faculty Hospital in Prague
12 First Faculty of Medicine Charles University [Prague]
13 Philipps Universität Marburg = Philipps University of Marburg
14 University of Bologna/Università di Bologna
15 UniCa - Università degli Studi di Cagliari = University of Cagliari
16 Department of Soil Science of Temperate Ecosystems, Georg August University of Goettingen, Buesgenweg 2, 37077, Goettingen, Germany
17 Georg-August-University = Georg-August-Universität Göttingen
18 Paracelsus-Elena-Klinik, Kassel, Germany.
19 Service de Neurologie [CHU Saint-Antoine]
20 Euromov DHM - EuroMov - Digital Health in Motion
21 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
22 UKM - University Hospital Münster - Universitaetsklinikum Muenster [Germany]
23 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
24 Jessa Ziekenhuis [Hasselt]
25 UGR - Universidad de Granada = University of Granada
26 Mayo Clinic
27 CHU Sainte Justine [Montréal]
28 Montreal General Hospital
29 NIH - National Institutes of Health [Bethesda]
Femke Dijkstra
Mineke Viaene
Bradley F Boeve
  • Function : Author
Guy A Rouleau
Ziv Gan-Or
  • Function : Author
  • PersonId : 1102060


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.
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Dates and versions

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



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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