Comprehensive Analysis of Familial Parkinsonism Genes in Rapid‐Eye‐Movement Sleep Behavior Disorder
Kheireddin Mufti, Uladzislau Rudakou, Eric Yu, Lynne Krohn, Jennifer A. Ruskey, Farnaz Asayesh, Sandra B. Laurent, Dan Spiegelman, Isabelle Arnulf, Michele T.M. Hu, Jacques Montplaisir, Jean‐François Gagnon, Alex Désautels, Yves Dauvilliers, Gian Luigi Gigli, Mariarosaria Valente, Francesco Janes, Birgit Högl, Ambra Stefani, Evi Holzknecht, Karel Šonka, David Kemlink, Wolfgang H. Oertel, Annette Janzen, Giuseppe Plazzi, Elena Antelmi, Michela Figorilli, Monica Puligheddu, Brit Mollenhauer, Claudia Trenkwalder, Friederike Sixel‐Döring, Valérie Cochen De Cock, Christelle Monaca, Anna Heidbreder, Luigi Ferini‐Strambi, Femke Dijkstra, Mineke Viaene, Beatriz Abril, Bradley F. Boeve, Ronald B. Postuma, Guy A. Rouleau, Ziv Gan‐Or
Abstract
BACKGROUND: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). OBJECTIVE: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. METHODS: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. RESULTS: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. CONCLUSION: Our results do not support a major role for variants in these genes in the risk of iRBD. © 2020 International Parkinson and Movement Disorder Society.