Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies

E Leitão; A Santini; B Cogne; M Essid; M Athanasiadou; CW LaFlamme; P Marijon; V Bernard; K Jousselin; N Chatron; G Barcia; B Keren; C Mignot; P Charles; T Besnard; R Paluch; JM de Sainte Agathe; EP Almanza Fuerte; S Sengupta; M Milh; F Ramond; T Allan; I An; C Araujo; S Arpin; C Austin-Tse; S Auvin; S Baer; N Bahi-Buisson; M Bak; M Barth; S Baulac; N Bednarek-Weirauch; M Begemann; MF Bennett; U Bensabath; S Bézieau; R Bhouri; M Biehler; TB Hammer; J Bogoin; E Bonanno; S Boussion; C Bris; A Brosseau-Beauvir; AL Bruel; A Briand-Suleau; J Buratti; T Celse; P Chambon; N Chemaly; B Chesneau; E Colin; M Colmard; C Colson; S Conrad; T Courtin; I Creveaux; AC Cullier; LT Dang; A de Saint Martin; C de Vanssay de Blavous Legendre; B Demeer; AS Denommé-Pichon; P Diekhoff; S DiTroia; M Doco-Fenzy; C Dubourg; C Dubucs; S Ducreux; L Dufour; R Duquet; B Durand; S El Chehadeh; M Elbracht; L Faivre; M Faoucher; A Faudet; S Forlani; M Fradin; P Gaignard; B Ganne; A Garde; J Géraud; D Gill; A Goldenberg; D Grabli; C Grisel; S Gueden; P Gueguen; AM Guerrot; A Guichet; TB Haack; N Härting; MG Häusler; S Heide; T Herget; B Héron; D Héron; J Herwig

Journal article

Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies

E Leitão, A Santini, B Cogne, M Essid, M Athanasiadou, CW LaFlamme, P Marijon, V Bernard, K Jousselin, N Chatron, G Barcia, B Keren, C Mignot, P Charles, T Besnard, R Paluch, JM de Sainte Agathe, EP Almanza Fuerte, S Sengupta, M Milh Show all

Nature Genetics | Published : 2026

DOI: 10.1038/s41588-026-02547-5

Abstract

Small nuclear RNAs (snRNAs) are essential components of the spliceosome. De novo variants in snRNA genes RNU4-2 (ReNU syndrome), RNU5B-1 and RNU2-2 have been linked to dominant neurodevelopmental disorders (NDDs), revealing a large unexpected contribution of noncoding RNA genes to genetic diseases. Here, through international collaborations, we analyze systematically 200 potentially functional snRNA genes in a French cohort of 34,329 people with rare disorders. We report RNU2-2 variants in 141 individuals, including 35 with recurrent dominant pathogenic variants and 91 affected members from 73 families with biallelic variants. Recessive RNU2-2 NDD is at least twice as frequent as the dominan..

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University of Melbourne Researchers

Mark Bennett Author

Amy Schneider Author

Michael Hildebrand Author

Ingrid Scheffer Author

Related Projects (1)

Translational research to transform care in the developmental and epileptic encephalopathies

Grants

Awarded by Deutsche Forschungsgemeinschaft (German Research Foundation)

Awarded by Eesti Teadusagentuur (Estonian Research Council)

Awarded by U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)

Awarded by Department of Health | National Health and Medical Research Council (NHMRC)

Awarded by EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)

Awarded by AXA Research Fund (Le Fonds AXA pour la Recherche)