ArticleEuropean journal of human genetics : EJHG2023
BRAT1-related disorders: phenotypic spectrum and phenotype-genotype correlations from 97 patients.
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Article in European journal of human genetics : EJHG, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- Diverse mediators of cancer predisposition uncovered by germline whole genome sequencing of unexplained familial cancers.medRxiv : the preprint server for health sciences · 2026Article
- Unprocessed U1 snRNAs as a biomarker of INTS11- and BRAT1-related neurodevelopmental disorders.Genome medicine · 2026Article
- Article
- Clinical and Neurodevelopmental Characteristics of Paralogous Gain-of-Function Variants at GRIA2 p.Gly792 and GRIA3 p.Gly803.Clinical genetics · 2025Article
- Epigenetic Impact of Sleep Timing in Children: Novel DNA Methylation Signatures via SWAG Analysis.International journal of molecular sciences · 2025Article
- Classification of Brain Magnetic Resonance Imaging Abnormalities and Spectrum of Neurological Findings in a Cohort with Copy Number Variation-Related Disorders.Molecular syndromology · 2025Article
- Distinguishing Genetic Alterations Versus (Epi)Mutations in Silver-Russell Syndrome and Focus on the IGF1R Gene.The Journal of clinical endocrinology and metabolism · 2025Article
- Elucidating the genomic basis of rare pediatric neurological diseases in Central Asia and Transcaucasia.Nature genetics · 2024Article
- NovelEpilepsy & behavior reports · 2024Article
- Why don't we all use genomic testing?European journal of human genetics : EJHG · 2023Article
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Authors and funding
90 authors at 20 institutions in 13 countries.
Camille EngelCentre de Génétique Humaine, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France. cengel@chu-besancon.fr.ORCID 0000-0003-1531-7628
Stéphanie ValenceService de Neurologie Pédiatrique, Hôpital Armand Trousseau, APHP Sorbonne Université, Paris, France.ORCID 0000-0003-4530-4537
Geoffroy DelplancqCentre de Génétique Humaine, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France.
Reza MaroofianDepartment of Neuromuscular Diseases UCL Queen Square Institute of Neurology, University College London, London, UK.
Andrea AccogliDepartment of Specialized Medicine, Division of Medical Genetics, McGill University Health Centre, Montreal, QC, Canada.
Emanuele AgoliniLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Fowzan S AlkurayaDepartment of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.ORCID 0000-0003-4158-341X
Valentina BaglioniDepartment of Human Neurosciences, Institute of Child and Adolescent Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Irene BagnascoDivision of Neuropsychiatry, Epilepsy Center for Children, Martini Hospital, 10141, Turin, Italy.
Mathilde Becmeur-LefebvreService de Génétique Clinique, CHR d'Orléans, Orléans, France.ORCID 0000-0002-9102-6884
Enrico BertiniUnit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.ORCID 0000-0001-9276-4590
Ingo BorggraefeDepartment of Pediatric Neurology, Developmental Medicine and Social Pediatrics, University of Munich, 80337, Munich, Germany.
Elise Brischoux-BoucherCentre de Génétique Humaine, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France.ORCID 0000-0002-4816-1431
Ange-Line BruelUMR 1231 GAD, Inserm, Université de Bourgogne Franche Comté, Dijon, France.ORCID 0000-0002-0526-465X
Alfredo BruscoDepartment of Medical Sciences, University of Torino, 10126, Turin, Italy.ORCID 0000-0002-8318-7231
Dalal K BubshaitDepartment of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Christelle CabrolCentre de Génétique Humaine, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France.
Maria Roberta CilioDepartment of Pediatrics, Division of Pediatric Neurology Saint-Luc University Hospital, and Institute of Neuroscience (IoNS), Catholic University of Louvain, Brussels, Belgium.
Marie-Coralie CornetDepartment of Pediatrics, Division of Neonatology, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5233-0800
Christine CoubesDépartement de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Hôpital Arnaud de Villeneuve, CHU de Montpellier, Montpellier, France.
Olivier DanhaiveDivision of Neonatology, Saint-Luc university Hospital, and Institut of Clinical and Experimental Research (IREC), Bruxelles, Belgium.
Valérie DelagueAix Marseille Univ, INSERM, Marseille Medical Genetics Center, MMG, Marseille, France.ORCID 0000-0003-2652-362X
Anne-Sophie Denommé-PichonUMR 1231 GAD, Inserm, Université de Bourgogne Franche Comté, Dijon, France.ORCID 0000-0002-8986-8222
Marilena Carmela Di GiacomoMedical Genetics Service and Laboratory of Cytogenetics, SIC Anatomia Patologica, "San Carlo" Hospital, 85100, Potenza, Italy.
Martine Doco-FenzyCHU Reims, Service de Génétique, Reims, France.
Hartmut EngelsInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.ORCID 0000-0003-1007-1809
Kirsten CremerInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Marion GérardClinical Genetics, Côte de Nacre University Hospital Center, Caen, France.
Joseph G GleesonUniversity of California San Diego, Department of Neurosciences, Rady Children's Institute for Genomic Medicine, San Diego, CA, 92037, USA.ORCID 0000-0002-6713-8018
Delphine HeronDepartment of Genetics, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne University, Paris, France.
Joanna GoffeneyService de neuropédiatrie, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France.
Anne GuimierService de Médecine Génomique des Maladies Rares, Hôpital Necker Enfants Malades, Institut Imagine et Université Paris-Cité, Paris, France.
Frederike L HarmsInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0003-2610-0600
Henry HouldenDepartment of Neuromuscular Diseases UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID 0000-0002-2866-7777
Michele IacominoUnit of Medical Genetics, IRCCS Instituto Giannina Gaslini, Genova, Italy.
Rauan KaiyrzhanovDepartment of Neuromuscular Diseases UCL Queen Square Institute of Neurology, University College London, London, UK.
Benjamin KamienGenetic Services of Western Australia, King Edward Memorial Hospital, Perth, WA, 6008, Australia.
Ehsan Ghayoor KarimianiDepartment of Molecular Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran.
Dror KrausDepartment of Neurology, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.
Paul KuentzUMR 1231 GAD, Inserm, Université de Bourgogne Franche Comté, Dijon, France.ORCID 0000-0003-2814-6303
Kerstin KutscheInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Damien LedererInstitute for Pathology and Genetics, 6040, Gosselies, Belgium.
Lauren MassinghamDivision of Medical Genetics, Department of Pediatrics, Hasbro Children's Hospital, Providence, RI, USA.
Cyril MignotAPHP, Sorbonne Université, Département de Génétique, Paris, France.
Déborah Morris-RosendahlClinical Genetics and Genomics, Royal Brompton and Harefield NHS Foundation Trust, London, UK.ORCID 0000-0002-7780-4707
Lakshmi NagarajanDepartment of Neurology, Perth Children's Hospital, Nedlands, WA, Australia.
Sylvie OdentService de Génétique Clinique, Centre Référence "Déficiences Intellectuelles de causes rares" (CRDI), Centre Référence Anomalies du développement (CLAD-Ouest), CHU Rennes, Univ Rennes, Rennes, France.
Clothilde OrmièresService de Médecine Génomique des Maladies Rares, Hôpital Necker Enfants Malades, Institut Imagine et Université Paris-Cité, Paris, France.
Jennifer Neil PartlowDivision of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
Laurent PasquierService de Génétique Clinique, Centre Référence "Déficiences Intellectuelles de causes rares" (CRDI), Centre Référence Anomalies du développement (CLAD-Ouest), CHU Rennes, Univ Rennes, Rennes, France.ORCID 0000-0003-3985-1286
Lynette PenneyDepartment of Pediatrics, IWK Health Centre, Dalhousie University, Halifax, NS, Canada.
Christophe PhilippeUMR 1231 GAD, Inserm, Université de Bourgogne Franche Comté, Dijon, France.ORCID 0000-0001-7098-6520
Gianluca PiccoloUOSD Neuro-oncology, IRCCS Giannina Gaslini, Genova, Italy.ORCID 0000-0003-2815-6288
Cathryn PoultonGenetic Services of Western Australia, King Edward Memorial Hospital, Perth, WA, 6008, Australia.
Audrey PutouxHospices Civils de Lyon, Service de Génétique, Bron, France.
Marlène RioService de Médecine Génomique des Maladies Rares, Hôpital Necker Enfants Malades, Institut Imagine et Université Paris-Cité, Paris, France.
Christelle RougeotHôpital Femme Mère Enfant, Service de Neuropédiatrie, Bron, France.
Vincenzo SalpietroDepartment of Neuromuscular Diseases UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID 0000-0003-0132-7921
Ingrid SchefferDepartment of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia.
Amy SchneiderDepartment of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia.ORCID 0000-0001-5260-7187
Siddharth SrivastavaDepartment of Neurology, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0001-7008-1879
Rachel StraussbergSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel.
Pasquale StrianoIRCCS Giannina Gaslini Institute, Genova, Italy.ORCID 0000-0002-6065-1476
Enza Maria ValenteDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.ORCID 0000-0002-0600-6820
Perrine VenotNeonatal Intensive Care Unit, Institut Alix de Champagne, Reims, France.
Laurent VillardAix Marseille Univ, INSERM, Marseille Medical Genetics Center, MMG, Marseille, France.ORCID 0000-0001-6657-5008
Antonio VitobelloUMR 1231 GAD, Inserm, Université de Bourgogne Franche Comté, Dijon, France.ORCID 0000-0003-3717-8374
Johanna WagnerDepartment of Pediatric Neurology, Developmental Medicine and Social Pediatrics, University of Munich, 80337, Munich, Germany.
Matias WagnerDepartment of Pediatric Neurology, Developmental Medicine and Social Pediatrics, University of Munich, 80337, Munich, Germany.ORCID 0000-0002-4454-8823
Maha S ZakiClinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.ORCID 0000-0001-7840-0002
Federizo ZaraIRCCS Giannina Gaslini Institute, Genova, Italy.
Gaetan LescaHospices Civils de Lyon, Service de Génétique, Bron, France.ORCID 0000-0001-7691-9492
Vahid Reza YassaeeGenomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mohammad MiryounesiDepartment of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Farzad Hashemi-GorjiGenomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.ORCID 0000-0002-9996-9406
Mehran BeiraghiDepartment of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Farah AshrafzadehDepartment of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Hamid GalehdariDepartment of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Christopher WalshDivision of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0002-0156-2238
Antonio NovelliLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.ORCID 0000-0002-9037-4297
Moritz TackeDepartment of Pediatric Neurology, Developmental Medicine and Social Pediatrics, University of Munich, 80337, Munich, Germany.
Dinara SadykovaAstana Medical University, Nur-Sultan, Kazakhstan.
Yerdan MaidyrovS. D. Asfendiyarov Kazakh National Medical University Almaty, Almaty, Kazakhstan.
Kairgali KoneevDepartment of Neurology and Neurosurgery, Asfendiyarov Kazakh National Medical University, Almaty, 050000, Kazakhstan.
Chingiz ShashkinDepartment of Neurology, The International Institute of Postraduate Education, Almaty, Kazakhstan.
Valeria CapraUnit of Medical Genetics, IRCCS Instituto Giannina Gaslini, Genova, Italy.
Mina ZamaniDepartment of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Lionel Van MaldergemCentre de Génétique Humaine, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France.
Lydie BurglenCentre de Référence des Malformations et Maladies Congénitales du Cervelet, Département de Génétique, AP-HP, Sorbonne Université, Hôpital Trousseau, Paris, France.ORCID 0000-0002-1119-6809
Juliette PiardCentre de Génétique Humaine, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France.ORCID 0000-0001-5244-5325
Inserm · FRIstituto Giannina Gaslini · ITQueen Mary University of London · GBSorbonne Université · FRBambino Gesù Children's Hospital · ITBoston Children's Hospital · USHôpital Necker-Enfants Malades · FRLudwig-Maximilians-Universität München · DEShahid Beheshti University of Medical Sciences · IRCentre Hospitalier Universitaire de Rennes · FRCliniques Universitaires Saint-Luc · BEKazakh National Medical University · KZKing Edward Memorial Hospital · AUMashhad University of Medical Sciences · IRShahid Chamran University of Ahvaz · IRTel Aviv University · ILUniversität Hamburg · DEUniversité Claude Bernard Lyon 1 · FRUniversity of Bonn · DEAstana Medical University · KZ
Funding
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4MInvestigating the Genetic Landscape of Cerebral PalsyK23NS119666 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI SRIVASTAVA, SIDDHARTH · 2021 to 2025
$1.1MNICHD NIH HHS P50 HD105351NINDS NIH HHS K23 NS119666
Abstract
BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations. Fifty-nine individuals presented with BRAT1-related RMFSL phenotype. Most of them had no psychomotor acquisition (100%), epilepsy (100%), microcephaly (91%), limb rigidity (93%), and died prematurely (93%). Thirty-eight individuals presented a non-lethal phenotype of BRAT1-related NEDCAS phenotype. Seventy-six percent of the patients in this group were able to walk and 68% were able to say at least a few words. Most of them had cerebellar ataxia (82%), axial hypotonia (79%) and cerebellar atrophy (100%). Genotype-phenotype correlations in our cohort revealed that biallelic nonsense, frameshift or inframe deletion/insertion variants result in the severe BRAT1-related RMFSL phenotype (46/46; 100%). In contrast, genotypes with at least one missense were more likely associated with NEDCAS (28/34; 82%). The phenotype of patients carrying splice variants was variable: 41% presented with RMFSL (7/17) and 59% with NEDCAS (10/17).
Indexed as
EpilepsyNeurodegenerative DiseasesAtrophyGenetic Association StudiesGenotypeHumansNuclear ProteinsPhenotypeBRAT1 protein, humanNuclear Proteins
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