ArticleNature genetics2026
De novo and inherited dominant variants in U4 and U6 snRNA genes cause retinitis pigmentosa.
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Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20citing papers in PubMed
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Who cites it
20 citing papers in PubMed.
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Whole-genome discovery of pathogenic snRNA variants and efficient extended-exome screening.iScience · 2026Article
- Guidance for clinical variant classification in genes for spliceosomal small nuclear RNAs.medRxiv : the preprint server for health sciences · 2026Article
- Past studies suggest potential therapies for newly discovered retinitis pigmentosa mutations in U6 and U4 snRNAs.RNA (New York, N.Y.) · 2026Article
- Retina-specific long non-coding RNAs associated with inherited retinal disease genes.Cellular and molecular life sciences : CMLS · 2026Article
- Review
- Article
- Whole-genome sequencing uncovers diverse genetic causes and phenotypic signatures in infantile nystagmus and albinism.NPJ genomic medicine · 2026Article
- Biallelic variants in the noncoding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes.Nature genetics · 2026Article
- Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies.Nature genetics · 2026Article
- Characterizing a Unique Retinal Phenotype in INTS11-Associated Neurodevelopmental Disorder.Investigative ophthalmology & visual science · 2026Article
- RP9 revisited; RP9 p.(H137L) remains a likely cause of dominant splicing factor-Retinitis Pigmentosa.European journal of human genetics : EJHG · 2026Article
- Neurodegenerative spliceosomopathies.Frontiers in cell and developmental biology · 2026Review
- The landscape of variants in pre-mRNA-processing factor genes in an Irish cohort.Genetics in medicine open · 2026Article
- Cause of vision loss discovered in overlooked genes.Nature · 2026Article
- Genome region aware CADD thresholds for noncoding variant prioritization.NAR genomics and bioinformatics · 2025Article
- Further evidence ofJournal of medical genetics · 2025Article
- Saturation genome editing ofmedRxiv : the preprint server for health sciences · 2025Article
- Expanding the mutational spectrum of ReNU syndrome: insights into 5' Stem-loop variants.European journal of human genetics : EJHG · 2025Article
- Epigenetic equilibrium in chromatinopathies: network instability in neurodevelopment.Frontiers in neurologyReview
Corrections and comments
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Authors and funding
188 authors.
Mathieu Quinodoz *Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
Kim Rodenburg *Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0003-0389-1518
Zuzana CvackovaLaboratory of RNA Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
Karolina KaminskaOphthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
Suzanne E de BruijnDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0003-2912-9265
Ana Belén Iglesias-RomeroOphthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
Erica G M BoonenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Mukhtar UllahOphthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
Nick ZomerDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Marc FolcherOphthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
Jacques BijonVitreous Retina Macula Consultants of New York, New York, NY, USA.
Lara K HoltesDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0009-0000-6337-4403
Stephen H TsangDepartments of Ophthalmology, Pathology & Cell Biology, Columbia Stem Cell Initiative, Vagelos College of Physicians and Surgeons Columbia University Irving Medical Center, New York, NY, USA.
Zelia CorradiDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
K Bailey FreundVitreous Retina Macula Consultants of New York, New York, NY, USA.ORCID 0000-0002-7888-9773
Stefanida ShliagaDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Daan M PannemanDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Rebekkah J Hitti-MalinDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Manir AliDivision of Molecular Medicine, Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK.ORCID 0000-0003-3204-3788
Ala'a AlTalbishiMolecular Biology Research Unit, St John Eye Hospital Group, Jerusalem, Palestine.
Sten AndréassonDepartment of Ophthalmology, University Hospital of Lund, Lund, Sweden.
Georg AnsariDepartment of Ophthalmology, University of Basel, Basel, Switzerland.
Gavin ArnoJC Self Research Institute, Greenwood Genetic Center, Greenwood, SC, USA.
Galuh D N AstutiDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Carmen AyusoDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.ORCID 0000-0002-9242-7065
Radha AyyagariDepartment of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.
Sandro BanfiMedical Genetics, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.ORCID 0000-0002-6541-8833
Eyal BaninHadassah Medical Center, Division of Ophthalmology, The Hebrew University of Jerusalem, Jerusalem, Israel.
Tahsin Stefan BarakatDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0003-1231-1562
Mirella T S BarboniDepartment of Ophthalmology, Semmelweis University, Budapest, Hungary.ORCID 0000-0002-0717-1852
Miriam BauwensCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Tamar Ben-YosefRappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Virginie BernardGCS Auragen, Plan France Medecine Genomique, Lyon, France.
David G BirchRetina Foundation of the Southwest, Dallas, TX, USA.ORCID 0000-0002-6594-2897
Pooja BiswasDepartment of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.
Fiona Blanco-KellyDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.
Beatrice BocquetInstitute for Neurosciences of Montpellier (INM), Montpellier University, INSERM, Montpellier, France.ORCID 0000-0002-6369-4818
Camiel J F BoonDepartment of Ophthalmology, Leiden University Medical Center (LUMC), Leiden, the Netherlands.
Kari BranhamDepartment of Ophthalmology and Human Genetics, University of Michigan, Ann Arbor, MI, USA.
Dominique Bremond-GignacDepartment of Ophthalmology, University Hospital Necker Enfants Malades, APHP, Paris Cité University, Paris, France.
Alexis Ceecee Britten-JonesDepartment of Optometry and Vision Sciences, The University of Melbourne, Melbourne, Victoria, Australia.ORCID 0000-0002-1101-2870
Kinga M BujakowskaOcular Genomics Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6809-9818
Cyril Burin des RoziersUMRS1138, Centre de Recherche des Cordeliers, Université Paris Cité, INSERM, Paris, France.
Elizabeth L CadenaDepartment of Epidemiology and Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Giacomo CalzettiVista Vision Eye Clinic, Brescia, Italy.ORCID 0000-0003-1391-9510
Francesca CancellieriOphthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
Luca CattaneoNeurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy.
Naomi ChaddertonInstitute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, The University of Dublin, Dublin, Ireland.
Peter Charbel IssaDepartment of Ophthalmology, TUM University Hospital, School of Medicine and Health, Technical University of Munich, Munich, Germany.ORCID 0000-0002-0351-6673
Luísa Coutinho-SantosServiço de Oftalmologia, Instituto de Oftalmologia Dr. Gama Pinto, Lisboa, Portugal.ORCID 0000-0002-6181-4505
Stephen P DaigerDepartment of Epidemiology and Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Elfride De BaereCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Marieke De BruyneCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.ORCID 0000-0001-6636-5537
Berta de la CerdaDepartment of Cell Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre, CABIMER, Seville, Spain.ORCID 0000-0001-5603-6473
John N De RoachAustralian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
Julie De ZaeytijdDepartment of Head and Skin, Ghent University, Ghent, Belgium.
Ronny DerksDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Claire-Marie DhaenensUniversité de Lille, INSERM U1172 - LilNCog - Lille Neuroscience & Cognition, Lille, France.
Lubica DudakovaDepartment of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.ORCID 0000-0003-4718-8955
Jacque L DuncanDepartment of Ophthalmology, University of California, San Francisco, Wayne and Gladys Valley Center for Vision, San Francisco, CA, USA.ORCID 0000-0002-9593-6412
G Jane FarrarInstitute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, The University of Dublin, Dublin, Ireland.
Nicolas FeltgenDepartment of Ophthalmology, University of Basel, Basel, Switzerland.
Beau J FennerDepartment of Medical Retina, Singapore National Eye Centre, Singapore, Singapore.ORCID 0000-0002-5356-7604
Lidia Fernández-CaballeroDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.
Juliana M Ferraz SallumDepartment of Ophthalmology, Federal University of São Paulo, UNIFESP, São Paulo, Brazil.ORCID 0000-0002-7206-4447
Simone GanaNeurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy.
Alejandro GarantoDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0001-5721-1560
Jessica C GardnerUCL Institute of Ophthalmology, University College London, London, UK.ORCID 0000-0002-7053-0707
Christian GilissenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0003-1693-9699
Roser Gonzàlez-DuarteDepartment of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain.
Kensuke GotoDepartment of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Sam Griffiths-JonesSchool of Biological Sciences, Division of Evolution, Infection, and Genomics, The University of Manchester, Manchester, UK.ORCID 0000-0001-6043-807X
Tobias B HaackInstitute for Medical Genetics and Applied Genomics, University of Tübingen, Institute for Ophthalmic Research, University Hospital Tübingen, Tübingen, Germany.ORCID 0000-0001-6033-4836
Lonneke Haer-WigmanDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Alison J HardcastleUCL Institute of Ophthalmology, University College London, London, UK.ORCID 0000-0002-0038-6770
Takaaki HayashiDepartment of Ophthalmology, The Jikei University School of Medicine, Minato-ku, Japan.ORCID 0000-0002-1535-0279
Elise HéonDepartment of Ophthalmology and Vision Sciences, Ocular Genetics Program, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID 0000-0003-4143-9311
Lies H HoefslootDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.ORCID 0009-0000-3444-9955
Alexander HoischenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0002-8072-4476
Josephine P HoltanDepartment of Ophthalmology, Oslo University Hospital, Oslo, Norway.ORCID 0000-0001-7731-0750
Carel B HoyngDepartment of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
Manuel Benjamin B IbanezDepartment of Ophthalmology, Section of Pediatric Ophthalmology, Strabismus, and Ocular Genetics, DOH Eye Center, East Avenue Medical Center, Quezon City, Philippines.
Chris F InglehearnDivision of Molecular Medicine, Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK.ORCID 0000-0002-5143-2562
Takeshi IwataDivision of Molecular and Cellular Biology, National Institute of Sensory Organs, NHO Tokyo Medical Center, Tokyo, Japan.ORCID 0000-0003-1447-0081
Brynjar O JenssondeCODE genetics, Amgen Inc., Reykjavik, Iceland.
Kaylie JonesRetina Foundation of the Southwest, Dallas, TX, USA.
Vasiliki KalatzisInstitute for Neurosciences of Montpellier (INM), Montpellier University, INSERM, Montpellier, France.ORCID 0000-0002-9626-8807
Smaragda KamakariDepartment of Inherited Retinal Dystrophies, Ophthalmic Genetics Group, OMMA, Ophthalmological Institute of Athens, Athens, Greece.ORCID 0000-0003-4723-5213
Marianthi KaraliMedical Genetics, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
Ulrich KellnerCenter for Rare Retinal Diseases, AugenZentrum Siegburg, MVZ Augenärztliches Diagnostik- und Therapiecentrum Siegburg GmbH, Siegburg, Germany.ORCID 0000-0001-5221-4631
Caroline C W KlaverDepartment of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
Krisztina KnézyDepartment of Ophthalmology, Semmelweis University, Budapest, Hungary.
Robert K KoenekoopDepartment of Pediatric Surgery, Division of Pediatric Ophthalmology, Montreal Children's Hospital, McGill University Health Center (MUHC), Montreal, Quebec, Canada.
Susanne KohlInstitute for Ophthalmic Research, Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany.ORCID 0000-0002-6438-6331
Taro KominamiDepartment of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Laura KühleweinUniversity Eye Hospital, Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany.ORCID 0000-0003-1906-8681
Tina M LameyAustralian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.ORCID 0000-0002-4608-4073
Rina LeibuDepartment of Ophthalmology, Rambam Health Care Campus, Haifa, Israel.
Bart P LeroyCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.ORCID 0000-0002-9899-2081
Petra LiskovaDepartment of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.ORCID 0000-0001-7834-8486
Irma LopezDepartment of Pediatric Surgery, Division of Pediatric Ophthalmology, Montreal Children's Hospital, McGill University Health Center (MUHC), Montreal, Quebec, Canada.
Victor R de J López-RodríguezDepartment of Genetics, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.ORCID 0009-0000-3770-9783
Quinten MahieuCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.ORCID 0000-0002-0850-1745
Omar A MahrooUCL Institute of Ophthalmology, University College London, London, UK.ORCID 0000-0003-1254-0832
Gaël ManesInstitute for Neurosciences of Montpellier (INM), Montpellier University, INSERM, Montpellier, France.
Luke MansardGCS Auragen, Plan France Medecine Genomique, Lyon, France.
M Pilar Martín-GutiérrezDepartment of Ophthalmology, Fundación Jiménez Díaz University Hospital, Madrid, Spain.
Nelson MartinsCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.ORCID 0009-0003-1801-7142
Laura MauringDepartment of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
Martin McKibbinDivision of Molecular Medicine, Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK.
Terri L McLarenAustralian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
Isabelle MeunierInstitute for Neurosciences of Montpellier (INM), Montpellier University, INSERM, Montpellier, France.
Michel MichaelidesUCL Institute of Ophthalmology, University College London, London, UK.
José M MillánInstituto de Investigación Sanitaria La Fe (IIS La Fe) and CIBERER, Valencia, Spain.
Kei MizobuchiDepartment of Ophthalmology, The Jikei University School of Medicine, Minato-ku, Japan.
Rajarshi MukherjeeDepartment of Ophthalmology, Leeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UK.ORCID 0000-0002-8707-6248
Zoltán Zsolt NagyDepartment of Ophthalmology, Semmelweis University, Budapest, Hungary.
Kornelia NevelingDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0009-0000-8055-5329
Monika OłdakDepartment of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.ORCID 0000-0002-4216-9141
Michiel OorsprongDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Yang PanDivision of Molecular and Cellular Biology, National Institute of Sensory Organs, NHO Tokyo Medical Center, Tokyo, Japan.
Anastasia PapachristouDepartment of Ophthalmology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Antonio PercesepeDepartment of Medicine and Surgery, Medical Genetics, University of Parma, Parma, Italy.ORCID 0000-0002-3268-6786
Maximilian PfauDepartment of Ophthalmology, University of Basel, Basel, Switzerland.
Eric A PierceOcular Genomics Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
Emily PlaceOcular Genomics Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
Raj RamesarUCT/MRC Precision and Genomic Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.ORCID 0000-0001-5688-1634
Francis RamondGCS Auragen, Plan France Medecine Genomique, Lyon, France.ORCID 0000-0003-4540-8096
Florence Andrée RasquinDepartment of Ophthalmology, HUB-Erasme Hospital, Brussels, Belgium.
Gillian I RiceSchool of Biological Sciences, Division of Evolution, Infection, and Genomics, The University of Manchester, Manchester, UK.ORCID 0000-0002-4223-0571
Lisa RobertsUCT/MRC Precision and Genomic Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.ORCID 0000-0001-6766-0255
María Rodríguez-HidalgoDepartment of Neuroscience, Biodonostia Health Research Institute, Donostia-San Sebastián, Spain.
Javier Ruiz-EderraDepartment of Neuroscience, Biodonostia Health Research Institute, Donostia-San Sebastián, Spain.
Ataf H SabirWest Midlands Clinical Genetics Unit, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.ORCID 0000-0003-4857-1964
Ai Fujita SajikiDepartment of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0000-0001-7474-9194
Ana Isabel Sánchez-BarberoDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.
Asodu Sandeep SarmaHadassah Medical Center, Division of Ophthalmology, The Hebrew University of Jerusalem, Jerusalem, Israel.
Riccardo SangermanoOcular Genomics Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
Cristina M SantosServiço de Oftalmologia, Instituto de Oftalmologia Dr. Gama Pinto, Lisboa, Portugal.ORCID 0000-0002-4751-2180
Margherita ScarpatoMedical Genetics, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.ORCID 0009-0006-7367-7911
Hendrik P N SchollDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Dror SharonHadassah Medical Center, Division of Ophthalmology, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID 0000-0002-1789-5811
Sabrina G SignoriniDepartment of Child Neurology and Psychiatry, IRCCS Mondino Foundation, Pavia, Italy.
Francesca SimonelliEye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Ana Berta SousaDepartment of Medical Genetics, ULS Santa Maria, Lisboa, Portugal.
Maria StefaniotouDepartment of Ophthalmology, School of Medicine, University of Ioannina, Ioannina, Greece.
Kari StefanssondeCODE genetics, Amgen Inc., Reykjavik, Iceland.ORCID 0000-0003-1676-864X
Katarina StinglUniversity Eye Hospital, Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany.
Akiko SugaDivision of Molecular and Cellular Biology, National Institute of Sensory Organs, NHO Tokyo Medical Center, Tokyo, Japan.
Patrick SulemdeCODE genetics, Amgen Inc., Reykjavik, Iceland.
Lori S SullivanDepartment of Epidemiology and Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0001-5723-6397
Viktória SzabóDepartment of Ophthalmology, Semmelweis University, Budapest, Hungary.ORCID 0009-0002-4055-6110
Jacek P SzaflikDepartment of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
Gita TaurinaMedical Genetics and Prenatal Diagnostics Clinic, Children's Clinical University Hospital, Riga, Latvia.ORCID 0000-0002-7101-6929
Alberta A H J ThiadensDepartment of Ophthalmology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0002-4911-9462
Carmel ToomesDivision of Molecular Medicine, Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK.
Viet H TranDepartment of Ophthalmology; Oculogenetics Unit, Jules Gonin University Hospital; University of Lausanne, Lausanne, Switzerland.
Miltiadis K TsilimbarisDepartment of Ophthalmology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Pavlina TsokaDepartment of Ophthalmology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Veronika VaclavikDepartment of Ophthalmology; Oculogenetics Unit, Jules Gonin University Hospital; University of Lausanne, Lausanne, Switzerland.
Marie VajterDepartment of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.ORCID 0000-0002-9590-9633
Sandra ValeinaEye Disease Clinic, Children's University Hospital Riga, Riga, Latvia.
Enza Maria ValenteNeurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy.ORCID 0000-0002-0600-6820
Casey ValentineUCT/MRC Precision and Genomic Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.ORCID 0009-0007-6907-4197
Rebeca ValeroDepartment of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain.
Sophie ValleixUMRS1138, Centre de Recherche des Cordeliers, Université Paris Cité, INSERM, Paris, France.
Joseph van AerschotDepartment of Ophthalmology, Pediatric Ophthalmology and Ophthalmogenetics, University Hospitals Leuven, Leuven, Belgium.ORCID 0009-0004-0605-9262
L Ingeborgh van den BornThe Rotterdam Eye Hospital, Rotterdam Ophthalmic Institute, Rotterdam, the Netherlands.
Mattias Van HeetveldeCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.ORCID 0000-0001-5758-0366
Virginie J M VerhoevenDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0001-7359-7862
Andrea L VincentDepartment of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Science, University of Auckland, Auckland, New Zealand.ORCID 0000-0002-4185-3267
Andrew R WebsterUCL Institute of Ophthalmology, University College London, London, UK.ORCID 0000-0001-6915-9560
Laura WhelanInstitute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, The University of Dublin, Dublin, Ireland.ORCID 0000-0002-0537-4349
Bernd WissingerInstitute for Ophthalmic Research, Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany.
Georgia G YiotiDepartment of Ophthalmology, School of Medicine, University of Ioannina, Ioannina, Greece.
Kazutoshi YoshitakeDivision of Molecular and Cellular Biology, National Institute of Sensory Organs, NHO Tokyo Medical Center, Tokyo, Japan.
Juan C ZentenoDepartment of Genetics, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
Roberta ZeuliMedical Genetics, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
Theresia ZulegerInstitute for Medical Genetics and Applied Genomics, University of Tübingen, Institute for Ophthalmic Research, University Hospital Tübingen, Tübingen, Germany.
Chaim LandauBonei Olam - Center for Rare Jewish Genetic Diseases, Brooklyn, NY, USA.ORCID 0000-0001-5876-1062
Allan I JacobPhysicians Dialysis, Miami, FL, USA.
Siying LinNational Institute of Health Research Biomedical Research Centre, Moorfields Eye Hospital, London, UK.ORCID 0000-0003-1122-8396
Frans P M CremersDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Winston LeeDepartment of Ophthalmology, Columbia University Irving Medical Center, New York, NY, USA.
Jamie M EllingfordSchool of Biological Sciences, Division of Evolution, Infection, and Genomics, The University of Manchester, Manchester, UK.ORCID 0000-0003-1137-9768
David StanekLaboratory of RNA Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.ORCID 0000-0002-5865-175X
Susanne RoosingDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. susanne.roosing@radboudumc.nl.ORCID 0000-0001-9038-0067
Carlo RivoltaOphthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.ORCID 0000-0002-0733-9950
Funding
NAC Attack, a phase-3, multicenter, randomized, placebo-controlled trial in patients with retinitis pigmentosaUG1EY033293 · NEI · JOHNS HOPKINS UNIVERSITY · PI Xiangrong Kong · 2022 to 2026
$18.1MRapid-Prototyping and Design CoreP30EY002162 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAMBA, DEEPAK ASHOK · 1985 to 2024
$16.8MPrecision Medicine for Inherited Retinal DegenerationsR01EY012910 · NEI · UNIVERSITY OF PENNSYLVANIA · PI Eric A Pierce · 1999 to 2026
$15.9MP30 Core Grant for Vision ResearchP30EY014104 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Janey L Wiggs · 2002 to 2026
$15.1MInstrumentation, Fabrication, and Design CoreP30EY019007 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Xin Zhang · 2010 to 2026
$12.9MTherapeutic gene editing and multimodal imaging in juvenile macular degeneration R24EY028758 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI AUDO , ISABELLE, SPARROW, JANET RUTHE · 2020 to 2024
$10.9MVision BiostatisticsP30EY022589 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LINDA M ZANGWILL · 2012 to 2026
$10.3MTranslational Gene Therapy for CNGB1 Retinitis PigmentosaR24EY027285 · NEI · MICHIGAN STATE UNIVERSITY · PI HAUSWIRTH, WILLIAM W, MICHALAKIS, STYLIANOS · 2018 to 2022
$8.6MToward mechanism- and gene-based therapies for retinal degenerationR01EY018213 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Stephen H Tsang · 2008 to 2026
$6.6MGene Silencing and Gene Editing in PhototransductionR01EY024698 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Stephen H Tsang · 2015 to 2026
$4.7MUnraveling the molecular pathology of retinal degeneration through single cell genomicsR01EY031663 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AYYAGARI, RADHA, FRAZER, KELLY A · 2021 to 2025
$3.3MEnhancing cone survival in retinitis pigmentosa through cell-specific therapeutic CRISPR editing of a roxadustat targetR01EY033770 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI JAMES Bryant HURLEY, Stephen H Tsang · 2022 to 2026
$2.6MNEI NIH HHS K99 EY036930NEI NIH HHS P30 EY002162NEI NIH HHS P30 EY014104NEI NIH HHS P30 EY019007NEI NIH HHS P30 EY022589NEI NIH HHS P30 EY037668NEI NIH HHS R01 EY012910NEI NIH HHS R01 EY018213NEI NIH HHS R01 EY024698NEI NIH HHS R01 EY030499NEI NIH HHS R01 EY030591NEI NIH HHS R01 EY031663NEI NIH HHS R01 EY033770NEI NIH HHS R01 EY035717NEI NIH HHS R24 EY027285NEI NIH HHS R24 EY028758NEI NIH HHS T32 EY026590NEI NIH HHS U01 EY030580NEI NIH HHS UG1 EY033286NEI NIH HHS UG1 EY033292NEI NIH HHS UG1 EY033293Wellcome Trust
Abstract
Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP spliceosomal complex. Variants in RNU4-2, which encodes U4, have recently been implicated in neurodevelopmental disorders. Here we show that heterozygous inherited and de novo variants in RNU4-2 and in four RNU6 paralogs (RNU6-1, RNU6-2, RNU6-8 and RNU6-9), which encode U6, recur in individuals with nonsyndromic retinitis pigmentosa (RP), a genetic disorder causing progressive blindness. These variants cluster within the three-way junction of the U4/U6 duplex, a site that interacts with tri-snRNP splicing factors also known to cause RP (PRPF3, PRPF8, PRPF31), and seem to affect snRNP biogenesis. Based on our cohort, deleterious variants in RNU4-2 and RNU6 paralogs may explain up to ~1.4% of otherwise undiagnosed RP cases. This study highlights the contribution of noncoding RNA genes to Mendelian disease and reveals pleiotropy in RNU4-2, where distinct variants underlie neurodevelopmental disorder and retinal degeneration.
Indexed as
Genes, DominantRetinitis PigmentosaRNA, Small NuclearEye ProteinsHumansPedigreeRibonucleoproteins, Small NuclearRibonucleoprotein, U4-U6 Small NuclearRNA-Binding ProteinsEye ProteinsPRPF31 protein, humanPRPF8 protein, humanRibonucleoproteins, Small NuclearRibonucleoprotein, U4-U6 Small NuclearRNA-Binding ProteinsRNA, Small NuclearU4 small nuclear RNAU6 small nuclear RNA
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What Socratic holds
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LicenceCC BY-NC-ND
Read underepoch 390
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.