{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Leitao E"],"funding":["NICHD NIH HHS","NHGRI NIH HHS","Wellcome Trust"],"pubmed_abstract":["Variants in spliceosomal small nuclear RNA (snRNA) genes <i>RNU4-2</i> (ReNU syndrome), <i>RNU5B-1</i>, and <i>RNU2-2</i> have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, previously overlooked role for noncoding snRNAs in human disease. Here, we systematically analysed 200 potentially functional snRNA genes in a French cohort comprising 26,911 individuals with rare disorders and through international collaborations. We identify <i>de novo</i> and biallelic variants in <i>RNU2-2</i> associated with both dominant and recessive NDDs in 126 individuals from 108 unrelated families. Recessive <i>RNU2-2</i> NDD is at least twice as frequent as the dominant NDD caused by n.4G>A and n.35A>G, and often arises from a <i>de novo</i> variant in <i>trans</i> "],"journal":["medRxiv : the preprint server for health sciences"],"pagination":["2025.09.02.25334923"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12424890"],"repository":["biostudies-literature"],"pubmed_title":["Systematic analysis of snRNA genes reveals frequent &lt;i&gt;RNU2-2&lt;/i&gt; variants in dominant and recessive developmental and epileptic encephalopathies."],"pmcid":["PMC12424890"],"funding_grant_id":["U24 HD090743","U01 HG011755","UM1 HG008900"],"pubmed_authors":["Bernard V","Rossi M","Jousselin K","Chehadeh SE","de Saint Martin A","O'Leary MC","Bensabath U","Richard AC","Gaignard P","Prouteau C","Thiyagarajah H","Bris C","Levy J","Dang LT","Kaya S","Rivier C","Leitao E","Rupin M","Lyonnet S","Gueguen P","Macdonald S","Lermine A","Faivre L","Chatron N","Zaki MS","Ziegler A","Nabbout R","de Sainte Agathe JM","Kurth I","Yammine T","Bogoin J","Grisel C","Baer S","Labalme A","Schluth-Bolard C","Seplyarskiy V","Stenton SL","Jacquette A","Heide S","Charenton C","Ducreux S","Faoucher M","Witkowski T","Geraud J","Cogne B","Ville D","Thevenon J","Keren B","Gill D","Sarrazin E","Denomme-Pichon AS","Faudet A","Laloy JS","Besnard T","Valleix S","Kirstetter R","Bruel AL","Colin E","Panagiotakaki E","Robin-Renaldo F","Dufour L","Begemann M","Saneto R","Sadleir LG","Goldenberg A","Pouzet A","Patat O","Waernessyckle A","Doco-Fenzy M","Weirauch NB","Hammer TB","Saugier-Veber P","Allan T","Hausler MG","Nava C","Messaoud O","Bonanno E","Lebrun M","Lesca G","Garde A","Bhouri R","Bak M","Chambon P","Poirsier C","Austin-Tse C","Bahi-Buisson N","Morel G","Courtin T","Fuerte EPA","Navarro V","Zaafrane-Khachnaoui K","O'Donnell-Luria A","Petit F","Nambot S","Nizon M","Weber Y","Rollier P","Odent S","Chesneau B","Gueden S","Buratti J","Lieffering N","Marijon P","Conrad S","Laugel V","Wieczorek D","Depienne C","Boussion S","Baulac S","Bramswig NC","Scheffer IE","Tharreau M","Jean-Marcais N","Heron B","An I","Heron D","Mansour-Hendili L","Ounap K","Isidor B","Sperelakis-Beedham B","Paluch R","Toulouse J","Araujo C","Milh M","Kaiser FJ","Gleeson JG","Dubourg C","Torun D","Barth M","Duquet R","Chemaly N","Harting N","Villeneuve N","Schneider A","Hildebrand MS","Charbonnier C","Charles P","Villard L","Ojeda NM","Planes M","Brosseau-Beauvir A","Leguern E","Olin V","Yadavilli M","LaFlamme CW","Whiffin N","Blanc P","Ganne B","Heulin M","Auvin S","Barcia G","Valence S","Renaud M","Mefford HC","Kuechler A","Stock F","Schaefer E","Athanasiadou M","Santini A","Piton A","Arpin S","Quemener-Redon S","Rio M","Biehler M","Bennett MF","Perrin-Sabourin L","Smol T","Ramond F","Vitobello A","Bezieau S","Lebre AS","Maraval J","Kraft F","Munnich A","Philippe C","Dubucs C","Houdayer C","Forlani S","Pais LS","Essid M","Bricquir FL","Roubertie A","Schumann I","Mignot C","Guerrot AM","Nowak F","Neale A","de Vanssay de Blavous Legendre C","Januel L","Nicolas G","Grabli D","Sengupta S","Krause J","Mattausch C","Sunyaev S","Durand B","Konyukh M","Colmard M","King C","Mortreux J","Nguyen L","Fradin M","Luthy K","Guichet A","Elbracht M","DiTroia S"],"additional_accession":[]},"is_claimable":false,"name":"Systematic analysis of snRNA genes reveals frequent &lt;i&gt;RNU2-2&lt;/i&gt; variants in dominant and recessive developmental and epileptic encephalopathies.","description":"Variants in spliceosomal small nuclear RNA (snRNA) genes <i>RNU4-2</i> (ReNU syndrome), <i>RNU5B-1</i>, and <i>RNU2-2</i> have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, previously overlooked role for noncoding snRNAs in human disease. Here, we systematically analysed 200 potentially functional snRNA genes in a French cohort comprising 26,911 individuals with rare disorders and through international collaborations. We identify <i>de novo</i> and biallelic variants in <i>RNU2-2</i> associated with both dominant and recessive NDDs in 126 individuals from 108 unrelated families. Recessive <i>RNU2-2</i> NDD is at least twice as frequent as the dominant NDD caused by n.4G>A and n.35A>G, and often arises from a <i>de novo</i> variant in <i>trans</i> ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-05-02T03:19:57.79Z","creation":"2026-05-02T03:11:56.369Z"},"accession":"S-EPMC12424890","cross_references":{"pubmed":["40950445"],"doi":["10.1101/2025.09.02.25334923"]}}