ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder.
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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. 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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20 citing papers in PubMed, 31 citations in OpenAlex.
- Genome sequencing for the diagnosis of intellectual disability as a paradigm for rare diseases in the French healthcare setting: the prospective DEFIDIAG study.Genome medicine · 2025Trial
- Leucettinib-21 decreases dosage effects of DYRK1A in human trisomy 21 induced pluripotent stem cell-derived neural cells.Disease models & mechanisms · 2026Article
- Leucettinib-21 decreases dosage effects of DYRK1A in human trisomy 21 iPSC-derived neural cells.bioRxiv : the preprint server for biology · 2026Article
- Episignature leads to diagnosis and reclassification of DYRK1A variant in a child with syndromic neurodevelopmental disorder: a case report.Frontiers in genetics · 2026Article
- Analysis Methods for Diagnosing Rare Neurodevelopmental Diseases with Episignatures: A Systematic Review of the Literature.Biomedicines · 2025Review
- Interneuron migration defects during corticogenesis contribute to Dyrk1a haploinsufficiency syndrome pathogenesis.Molecular psychiatry · 2025Article
- The role of Goldilocks protein kinase DYRK1A in embryonic development.Developmental biology · 2025Review
- DYRK1A roles in human neural progenitors.Frontiers in neuroscience · 2025Article
- Clinical and molecular overlap between nucleotide excision repair (NER) disorders andFrontiers in neuroscience · 2025Article
- Loss of the DYRK1A Protein Kinase Results in the Reduction in Ribosomal Protein Gene Expression, Ribosome Mass and Reduced Translation.Biomolecules · 2023Article
- Identification of FAM53C as a cytosolic-anchoring inhibitory binding protein of the kinase DYRK1A.Life science alliance · 2023Article
- New insights into the roles for DYRK family in mammalian development and congenital diseases.Genes & diseases · 2023Review
- ANKRD11 pathogenic variants and 16q24.3 microdeletions share an altered DNA methylation signature in patients with KBG syndrome.Human molecular genetics · 2023Article
- An HNRNPK-specific DNA methylation signature makes sense of missense variants and expands the phenotypic spectrum of Au-Kline syndrome.American journal of human genetics · 2022Article
- The Omnipresence of DYRK1A in Human Diseases.International journal of molecular sciences · 2022Review
- Social motivation a relative strength in DYRK1A syndrome on a background of significant speech and language impairments.European journal of human genetics : EJHG · 2022Article
- Differential maturation and chaperone dependence of the paralogous protein kinases DYRK1A and DYRK1B.Scientific reports · 2022Article
- Clinical Utility of a Unique Genome-Wide DNA Methylation Signature forInternational journal of molecular sciences · 2022Article
- New insights into the regulation ofFrontiers in neuroscience · 2022Article
- Anatomy of DNA methylation signatures: Emerging insights and applications.American journal of human genetics · 2021Review
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Authors and funding
70 authors at 20 institutions in 4 countries.
Jérémie CourraudInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Eric Chater-DiehlGenetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Benjamin DurandInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Marie VincentService de Génétique Médicale, CHU de Nantes & Inserm, CNRS, Université de Nantes, l'institut du thorax, Nantes, France.
Maria Del Mar Muniz MorenoInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Imene BoujelbeneInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Nathalie DrouotInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Loréline GenschikInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Elise SchaeferService de Génétique Médicale, IGMA, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Mathilde NizonService de Génétique Médicale, CHU de Nantes & Inserm, CNRS, Université de Nantes, l'institut du thorax, Nantes, France.
Bénédicte GerardUnité de Génétique Moléculaire, IGMA, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.
Marc AbramowiczService of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.
Benjamin CognéService de Génétique Médicale, CHU de Nantes & Inserm, CNRS, Université de Nantes, l'institut du thorax, Nantes, France.
Lucas BronickiDepartment of Genetics, CHEO, Ottawa, ON, Canada.
Lydie BurglenCentre de référence des malformations et maladies congénitales du cervelet et Département de génétique et embryologie médicale, APHP, Sorbonne Université, Hôpital Armand Trousseau, Paris, France.
Magalie BarthPediatrics & Biochemistry and Genetics, Department, Angers Hospital, Angers, France.
Perrine CharlesGenetic Department, University Hospital Pitié-Salpêtrière, AP-HP, Paris, France.
Estelle ColinPediatrics & Biochemistry and Genetics, Department, Angers Hospital, Angers, France.
Christine CoubesDépartement de Génétique Médicale maladies rares et médecine personnalisée, Centre de Référence Maladies Rares Anomalies du Développement, Hôpital Arnaud de Villeneuve, Université Montpellier, Montpellier, France.
Albert DavidService de Génétique Médicale, CHU de Nantes & Inserm, CNRS, Université de Nantes, l'institut du thorax, Nantes, France.
Bruno DelobelCentre de Génétique Chromosomique, GHICL, Hôpital Saint Vincent de Paul, Lille, France.
Florence DemurgerService de Génétique, CH Bretagne Atlantique-Vannes, Vannes, France.
Sandrine PassemardDépartement de Génétique, Hôpital Universitaire Robert Debré, APHP, Paris, France.
Anne-Sophie DenomméCentre de Génétique et Centre de Référence Anomalies du développement et Syndromes malformatifs, Hôpital d'Enfants and INSERM UMR1231 GAD, FHU TRANSLAD, CHU de Dijon, Dijon, France.
Laurence FaivreCentre de Génétique et Centre de Référence Anomalies du développement et Syndromes malformatifs, Hôpital d'Enfants and INSERM UMR1231 GAD, FHU TRANSLAD, CHU de Dijon, Dijon, France.
Claire FegerUnité de Génétique Moléculaire, IGMA, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.
Mélanie FradinCentre de Référence Maladies Rares, Unité Fonctionnelle de Génétique Médicale, CHU, Rennes, France.
Christine FrancannetService de Génétique médicale, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
David GenevieveDépartement de Génétique Médicale maladies rares et médecine personnalisée, Centre de Référence Maladies Rares Anomalies du Développement, Hôpital Arnaud de Villeneuve, Université Montpellier, Montpellier, France.
Alice GoldenbergNormandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and Reference Center for Developmental Disorders, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France.
Anne-Marie GuerrotNormandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and Reference Center for Developmental Disorders, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France.
Bertrand IsidorService de Génétique Médicale, CHU de Nantes & Inserm, CNRS, Université de Nantes, l'institut du thorax, Nantes, France.
Katrine M JohannesenDepartment of Epilepsy Genetics and Personalized Treatment, The Danish Epilepsy Centre, Dianalund, Denmark.
Boris KerenGenetic Department, University Hospital Pitié-Salpêtrière, AP-HP, Paris, France.
Maria KibækDepartment of Clinical Genetics, Odense Denmark Hospital, Odense University Hospital, Odense, Denmark.
Paul KuentzCentre de Génétique et Centre de Référence Anomalies du développement et Syndromes malformatifs, Hôpital d'Enfants and INSERM UMR1231 GAD, FHU TRANSLAD, CHU de Dijon, Dijon, France.
Michèle Mathieu-DramardService de Génétique Clinique, Centre de référence maladies rares, CHU d'Amiens-site Sud, Amiens, France.
Bénédicte DemeerService de Génétique Clinique, Centre de référence maladies rares, CHU d'Amiens-site Sud, Amiens, France.
Julia MetreauAPHP, Service de neurologie pédiatrique, Hôpital Universitaire Bicetre, Le Kremlin-Bicetre, France.
Rikke Steensbjerre MøllerDepartment of Epilepsy Genetics and Personalized Treatment, The Danish Epilepsy Centre, Dianalund, Denmark.
Sébastien MouttonCentre de Génétique et Centre de Référence Anomalies du développement et Syndromes malformatifs, Hôpital d'Enfants and INSERM UMR1231 GAD, FHU TRANSLAD, CHU de Dijon, Dijon, France.
Laurent PasquierCentre de Référence Maladies Rares, Unité Fonctionnelle de Génétique Médicale, CHU, Rennes, France.
Kristina Pilekær SørensenDepartment of Clinical Genetics, Odense Denmark Hospital, Odense University Hospital, Odense, Denmark.
Laurence PerrinDepartment of Genetics, Robert Debré Hospital, AP-HP, Paris, France.
Mathilde RenaudService de Génétique Clinique et de Neurologie, Hôpital Brabois Enfants, Nancy, France.
Pascale SaugierNormandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and Reference Center for Developmental Disorders, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France.
Marlène RioDepartment of medical genetics and reference centre for rare intellectual disabilities, INSERM UMR 1163, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker Enfants Malades Hospital, Paris, France.
Joane SvaneDepartment of Clinical Genetics, Odense Denmark Hospital, Odense University Hospital, Odense, Denmark.
Julien ThevenonDepartment of Genetics and Reproduction, Centre Hospitalo-Universitaire Grenoble-Alpes, Grenoble, France.
Frédéric Tran Mau ThemCentre de Génétique et Centre de Référence Anomalies du développement et Syndromes malformatifs, Hôpital d'Enfants and INSERM UMR1231 GAD, FHU TRANSLAD, CHU de Dijon, Dijon, France.
Cathrine Elisabeth TronhjemDepartment of Clinical Genetics, Odense Denmark Hospital, Odense University Hospital, Odense, Denmark.
Antonio VitobelloCentre de Génétique et Centre de Référence Anomalies du développement et Syndromes malformatifs, Hôpital d'Enfants and INSERM UMR1231 GAD, FHU TRANSLAD, CHU de Dijon, Dijon, France.
Valérie LayetConsultations de génétique, Groupe Hospitalier du Havre, Le Havre, France.
Stéphane AuvinCenter for rare epilepsies & epilepsy unit Robert-Debré Hospital, APHP, & INSERM NeuroDiderot, Université de Paris, Paris, France.
Khaoula KhachnaouiUniversité Côte d'Azur, Inserm U1081, CNRS UMR7284, IRCAN, CHU de Nice, Nice, France.
Marie-Christine BirlingICS, Mouse Clinical Institute, Illkirch-Graffenstaden, France.
Séverine DrunatDépartement de Génétique, Hôpital Universitaire Robert Debré, Paris, France.
Allan BayatDepartment of Clinical Genetics, Odense Denmark Hospital, Odense University Hospital, Odense, Denmark.
Christèle DubourgLaboratoire de Génétique Moléculaire, CHU Pontchaillou, UMR 6290 CNRS, IGDR, Faculté de Médecine, Université de Rennes 1, Rennes, France.
Salima El ChehadehUnité de Génétique Moléculaire, IGMA, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.
Christina FagerbergDepartment of Clinical Genetics, Odense Denmark Hospital, Odense University Hospital, Odense, Denmark.
Cyril MignotPediatrics & Biochemistry and Genetics, Department, Angers Hospital, Angers, France.
Michel GuipponiService of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.
Thierry BienvenuMolecular Genetics Laboratory, Cochin Hospital, APHP.Centre-Université de Paris, and INSERM UMR 1266, Institut de Psychiatrie et de Neurosciences de Paris, Paris, France.
Yann HeraultInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Julie ThompsonComplex Systems and Translational Bioinformatics (CSTB), ICube laboratory-CNRS, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France.
Marjolaine WillemsDépartement de Génétique Médicale maladies rares et médecine personnalisée, Centre de Référence Maladies Rares Anomalies du Développement, Hôpital Arnaud de Villeneuve, Université Montpellier, Montpellier, France.
Jean-Louis MandelInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Rosanna WeksbergGenetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Amélie PitonInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. piton@igbmc.fr.
Centre National de la Recherche Scientifique · FRInserm · FROdense University Hospital · DKHôpitaux Universitaires de Strasbourg · FRSorbonne Université · FRUniversité d'Angers · FRUniversité de Montpellier · FRAssistance Publique – Hôpitaux de Paris · FRCentre Hospitalier Universitaire Amiens-Picardie · FRCentre Hospitalier Universitaire de Rennes · FRUniversity Hospital of Geneva · CHUniversity of Southern Denmark · DKAgricultural Research Institute of Ontario · CABicêtre Hospital · FRCentre hospitalier Bretagne Atlantique · FRCentre Hospitalier Universitaire de Clermont-Ferrand · FRCentre Hospitalier Universitaire de Grenoble · FRDélégation Paris 5 · FRGroupe Hospitalier de l'Institut Catholique de Lille · FRGroupe Hospitalier du Havre · FR
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDYRK1A syndrome is among the most frequent monogenic forms of intellectual disability (ID). We refined the molecular and clinical description of this disorder and developed tools to improve interpretation of missense variants, which remains a major challenge in human genetics.
methodsWe reported clinical and molecular data for 50 individuals with ID harboring DYRK1A variants and developed (1) a specific DYRK1A clinical score; (2) amino acid conservation data generated from 100 DYRK1A sequences across different taxa; (3) in vitro overexpression assays to study level, cellular localization, and kinase activity of DYRK1A mutant proteins; and (4) a specific blood DNA methylation signature.
resultsThis integrative approach was successful to reclassify several variants as pathogenic. However, we questioned the involvement of some others, such as p.Thr588Asn, still reported as likely pathogenic, and showed it does not cause an obvious phenotype in mice.
conclusionOur study demonstrated the need for caution when interpreting variants in DYRK1A, even those occurring de novo. The tools developed will be useful to interpret accurately the variants identified in the future in this gene.
Indexed as
Intellectual DisabilityMicrocephalyProtein Serine-Threonine KinasesProtein-Tyrosine KinasesAnimalsDyrk KinasesHumansMicePhenotypeDyrk KinasesProtein Serine-Threonine KinasesProtein-Tyrosine Kinases
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