OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: LRRK2 protective haplotype and full sequencing study in REM sleep behavior disorder.

PuSH - Publication Server of Helmholtz Zentrum München

Ouled Amar Bencheikh, B.* ; Ruskey, J.A.* ; Arnulf, I.* ; Dauvilliers, Y.* ; Monaca, C.C.* ; De Cock, V.C.* ; Gagnon, J.F.* ; Spiegelman, D.* ; Hu, M.T.M.* ; Högl, B.* ; Stefani, A.* ; Ferini-Strambi, L.* ; Plazzi, G.* ; Antelmi, E.* ; Young, P.* ; Heidbreder, A.* ; Mollenhauer, B.* ; Sixel-Döring, F.* ; Trenkwalder, C.* ; Oertel, W.H. ; Montplaisir, J.Y.* ; Postuma, R.B.* ; Rouleau, G.A.* ; Gan-Or, Z.*

LRRK2 protective haplotype and full sequencing study in REM sleep behavior disorder.

Parkinsonism Relat. Disord. 52, 98-101 (2018)
Postprint DOI PMC
Open Access Green
Background: Individuals with rapid eye movement (REM)-sleep behavior disorder (RBD) are likely to progress to synucleinopathies, mainly Parkinson's disease (PD), dementia with Lewy-bodies (DLB) and multiple system atrophy (MSA). The genetics of RBD only partially overlaps with PD and DLB, and the role of LRRK2 variants in risk for RBD is still not clear.Methods: The full coding sequence, exon-intron boundaries and 5' and 3' untranslated regions of LRRK2 were sequenced using targeted next-generation sequencing. A total of 350 RBD patients and 869 controls were sequenced, and regression and burden models were used to examine the association between LRRK2 variants and RBD.Results: No pathogenic mutations that are known to cause PD were identified in RBD patients. The p.N551K-p.R1398H-p.K1423K haplotype was associated with a reduced risk for RBD (OR = 0.66, 95% CI 0.44-0.98, p = 0.0055 for the tagging p.N551K substitution). A common variant, p.S1647T, was nominally associated with risk for RBD (OR = 1.28, 95% Cl 1.05-1.56, p = 0.029). Burden analysis identified associations with domains and exons that were derived by the variants of the protective haplotype, and no burden of other rare variants was identified.Conclusions: Carriers of the LRRK2 p.N551K-p.R1398H-p.K1423K haplotype have a reduced risk for developing RBD, yet PD-causing mutations probably have minor or no role in RBD. Additional work is needed to confirm these results and to identify the mechanism associated with reduced risk for RBD. (C) 2018 Elsevier Ltd. All rights reserved.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Rem Sleep Behavior Disorder ; Parkinson Disease ; Genetics ; Lrrk2; Glucocerebrosidase Mutations; Parkinsons-disease; Exonic Variants; Lewy Bodies; Multicenter; Dementia; Risk
ISSN (print) / ISBN 1353-8020
e-ISSN 1873-5126
Journal Parkinsonism & Related Disorders
Quellenangaben Volume: 52, Issue: , Pages: 98-101 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)