Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci

Aditya Ambati (1) , Ryan Hillary (1) , Smaranda Leu-Semenescu (2, 2) , Hanna Ollila (1) , Ling Lin (1) , Emmanuel During (1) , Neal Farber , Thomas Rico (1) , Juliette Faraco (1) , Eileen Leary (1) , Andrea Goldstein-Piekarski (1, 3) , Yu-Shu Huang (4) , F. Han (5) , Yakov Sivan (6) , Michel Lecendreux (7, 2) , Pauline Dodet (2) , Makoto Honda (8) , Natan Gadoth (9) , Sona Nevsimalova (10) , Fabio Pizza (11, 12) , Takashi Kanbayashi (13) , Rosa Peraita-Adrados (14) , Guy Leschziner (15, 16) , Rosa Hasan (17) , Francesca Canellas , Kazuhiko Kume (18) , Makrina Daniilidou (19, 20) , Patrice Bourgin (21) , David Rye (22) , José Vicario , Birgit Hogl (23) , Seung Chul Hong (24) , Guiseppe Plazzi (11, 12) , Geert Mayer (25) , Anne Marie Landtblom (19, 20) , Yves Dauvilliers (26, 27) , Isabelle Arnulf (2) , Emmanuel Jean-Marie Mignot (1)

1 Stanford University
2 CHU Pitié-Salpêtrière [AP-HP]
3 Veterans Affairs Palo Alto Healthcare System
4 CGMH - Chang Gung Memorial Hospital [Taipei]
5 Peking University [Beijing]
6 Sackler Faculty of Medicine
7 Hôpital Robert Debré
8 TMIMS - Tokyo Metropolitan Institute of Medical Science
9 Tel Aviv Sourasky Medical Center [Te Aviv]
10 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
11 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
12 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
13 Université de Tsukuba = University of Tsukuba
14 Hospital General Universitario "Gregorio Marañón" [Madrid]
15 Guy's Hospital [London]
16 King‘s College London
17 USP - Universidade de São Paulo = University of São Paulo
18 Nagoya City University [Nagoya, Japan]
19 Uppsala University Hospital
20 Linköping university hospital
21 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
22 Emory University [Atlanta, GA]
23 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
24 Catholic University of Korea
25 Philipps Universität Marburg = Philipps University of Marburg
26 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
27 INM - Institut des Neurosciences de Montpellier

Significance Genetic markers in TRANK1 gene and its vicinity have been weakly associated with bipolar disorder and schizophrenia (10% increased risk). We found that the same polymorphisms are associated with Kleine-Levin syndrome (50% increased risk), a rare sleep disorder characterized by recurrent episodes of severe hypersomnia and cognitive abnormalities. Response to lithium treatment is suggestive of a pathophysiological overlap between KLS and bipolar disorder. The study also shows that variants in the TRANK1 gene region may predispose to KLS when patients have had a difficult birth, suggesting that TRANK1 gene region modulates newborns’ response to brain injury, with consequences for mental and neurological health in adulthood. Another possibility may be that the polymorphism impacts birth and KLS.

Mots clés: GWAS; Kleine-Levin syndrome; Bipolar disorder; Birth difficulties; Hypersomnia

Domaines: Sciences du Vivant [q-bio]

Aditya Ambati, Ryan Hillary, Smaranda Leu-Semenescu, Hanna Ollila, Ling Lin, et al.. Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci. Proceedings of the National Academy of Sciences of the United States of America, 2021, 118 (12), pp.e2005753118. ⟨10.1073/pnas.2005753118⟩. ⟨hal-03670258⟩