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

Open access

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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