{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:52:37Z","timestamp":1791359557169,"version":"4.3.1"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    The\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    (Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A) gene is located on human chromosome 21 (HSA21) within the Down Syndrome Critical Region (DSCR). As a protein kinase,\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    is involved in the regulation of the cell cycle, cell growth, transcription, and cellular communication. It also plays essential roles in embryonic and neuronal development, and in disease pathogenesis. Dysregulation of\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    has been associated with several human disorders, including\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    syndrome, caused by\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    haploinsufficiency (i.e., one functional copy of the gene) and Down syndrome (DS), caused by trisomy 21 (i.e., three functional copies of the gene).\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    is an extremely dosage-sensitive gene and is considered one of the \u201cGoldilocks\u201d genes, for which both increased and decreased gene dosage can lead to pathological phenotypes. Interestingly, these two syndromes share several overlapping clinical features. This apparent paradox represents\/highlights a major gap in our current understanding of\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    function and raises important biological questions. In this review, we summarise the most important findings related to both DYRK1A syndrome and Down syndrome, as well as the available human cellular and animal models that provide valuable platforms for future research. To obtain a comprehensive understanding of\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    role, it is necessary to integrate data from multiple experimental systems and sources. Such an integrated approach will facilitate the identification of novel therapeutic targets and support the development of treatments that may ultimately advance to clinical trials.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1963992","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:20:26Z","timestamp":1791357626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["DYRK1A \u2013 a gene dose paradox"],"prefix":"10.3389","volume":"14","author":[{"given":"Ante","family":"Ple\u0107a\u0161","sequence":"first","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Gough","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Kun\u0161tek","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Veterinary Medicine, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirna","family":"Babi\u0107","sequence":"additional","affiliation":[{"name":"Vara\u017edin General Hospital","place":["Vara\u017edin, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife","family":"Murray","sequence":"additional","affiliation":[{"name":"ARUK-UCL Drug Discovery Institute, Faculty of Brain Sciences, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Ni\u017eeti\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Ali\u0107","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Zagreb","place":["Zagreb, Croatia"]},{"name":"Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/GENO.1998.5335","article-title":"10 years of genomics, chromosome 21, and Down syndrome","volume":"51","author":"Antonarakis","year":"1998","journal-title":"Genomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41572-019-0143-7","article-title":"Down syndrome","volume":"6","author":"Antonarakis","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B3","doi-asserted-by":"publisher","first-page":"770359","DOI":"10.3389\/FGENE.2021.770359","article-title":"Structural characterization of the highly restricted Down syndrome critical region on 21q22.13: New KCNJ6 and DSCR4 transcript isoforms","volume":"12","author":"Antonaros","year":"2021","journal-title":"Front. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"54285","DOI":"10.1371\/journal.pone.0054285","article-title":"Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: possible role in Down syndrome","volume":"8","author":"Arque","year":"2013","journal-title":"PLoS ONE"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.3390\/genes12111833","article-title":"Dyrk1a from gene function in development and physiology to dosage correction across life span in Down syndrome","volume":"12","author":"Atas-Ozcan","year":"2021","journal-title":"Genes"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e71498","DOI":"10.1002\/ALZ.71498","article-title":"Age-related behavioral and molecular landmarks in new mouse models for studying Alzheimer\u2019s disease in Down syndrome","volume":"22","author":"Baniowska","year":"2026","journal-title":"Alzheimer\u2019s and Dementia The Journal Alzheimer\u2019s Assoc."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e24502","DOI":"10.7554\/ELIFE.24502","article-title":"Inhibition of DYRK1A disrupts neural lineage specificationin human pluripotent stem cells","volume":"6","author":"Bellmaine","year":"2017","journal-title":"eLife"},{"key":"B8","doi-asserted-by":"publisher","first-page":"43331","DOI":"10.1038\/srep43331","article-title":"Efficient and rapid generation of large genomic variants in rats and mice using CRISMERE","volume":"7","author":"Birling","year":"2017","journal-title":"Sci. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/S41419-026-08464-Z","article-title":"Impaired BDNF-TrkB trafficking and signalling in Down syndrome basal forebrain neurons","volume":"17","author":"Blackburn","year":"2026","journal-title":"Cell Death and Disease"},{"key":"B10","doi-asserted-by":"publisher","first-page":"175","DOI":"10.5966\/SCTM.2012-0117","article-title":"Concise review: new paradigms for Down syndrome research using induced pluripotent stem cells: tackling complex human genetic disease","volume":"2","author":"Briggs","year":"2013","journal-title":"Stem Cells Transl. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1428146","DOI":"10.3389\/FNBEH.2024.1428146","article-title":"Dissecting the contribution of human chromosome 21 syntenic regions to recognition memory processes in adult and aged mouse models of Down syndrome","volume":"18","author":"Canonica","year":"2024","journal-title":"Front. Behavioral Neuroscience"},{"key":"B12","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/J.AJHG.2008.08.012","article-title":"DYRK1A-dosage imbalance perturbs NRSF\/REST levels, deregulating pluripotency and embryonic stem cell fate in Down syndrome","volume":"83","author":"Canzonetta","year":"2008","journal-title":"Am. Journal Human Genetics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/J.MOLCEL.2013.09.009","article-title":"Dosage of Dyrk1a shifts cells within a p21-Cyclin D1 signaling map to control the decision to enter the cell cycle","volume":"52","author":"Chen","year":"2013","journal-title":"Mol. Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1626062","DOI":"10.3389\/FNINS.2025.1626062","article-title":"DYRK1A in the physiology and pathology of the neuron-astrocyte axis","volume":"19","author":"Cisternas","year":"2025","journal-title":"Front. Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1038\/s41436-021-01263-1","article-title":"Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder","volume":"23","author":"Courraud","year":"2021","journal-title":"Genet. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1533253","DOI":"10.3389\/FNINS.2025.1533253","article-title":"DYRK1A roles in human neural progenitors","volume":"19","author":"Courraud","year":"2025","journal-title":"Front. Neurosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1007\/S00335-011-9356-0","article-title":"Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse lines: relevance for modeling Down syndrome","volume":"22","author":"Duchon","year":"2011","journal-title":"Mammalian Genome Official J. Int. Mammalian Genome Soc."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e970048","DOI":"10.4161\/23723548.2014.970048","article-title":"DYRK1A: the double-edged kinase as a protagonist in cell growth and tumorigenesis","volume":"2","author":"Fern\u00e1ndez-Mart\u00ednez","year":"2015","journal-title":"Mol. and Cell. Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"103345","DOI":"10.1016\/j.scr.2024.103345","article-title":"Generation of a human induced pluripotent stem cell line (FDCHi012-A) from a patient with DYRK1A-related intellectual disability syndrome carrying DYRK1A mutation (C.1024G > T)","volume":"76","author":"Ge","year":"2024","journal-title":"Stem Cell Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1016\/J.STEMCR.2022.05.001","article-title":"Altered patterning of trisomy 21 interneuron progenitors","volume":"17","author":"Giffin-Rao","year":"2022","journal-title":"Stem Cell Reports"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1803346","DOI":"10.3389\/FNINS.2026.1803346\/TEXT","article-title":"Editorial: advances in DYRK1A syndrome: underlying mechanisms, disease models, and novel therapeutic approaches","volume":"20","author":"Glass","year":"2026","journal-title":"Front. Neurosci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/J.NBD.2012.01.007","article-title":"DYRK1A: a master regulatory protein controlling brain growth","volume":"46","author":"Guedj","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/J.STEMCR.2016.08.003","article-title":"Molecular characterization of Down syndrome embryonic stem cells reveals a role for RUNX1 in neural differentiation","volume":"7","author":"Halevy","year":"2016","journal-title":"Stem Cell Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"RP109708","DOI":"10.7554\/ELIFE.109708","article-title":"The FAM53C\/DYRK1A axis regulates the G1\/S transition of the cell cycle","volume":"14","author":"Hammond","year":"2026","journal-title":"eLife"},{"key":"B25","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1017\/S1355617718000206","article-title":"Pediatric brain development in Down syndrome: a field in its infancy","volume":"24","author":"Hamner","year":"2018","journal-title":"J. Int. Neuropsychological Soc. JINS"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1101\/2025.07.21.665861","article-title":"Hippocampal circuit-specific enhancement of GABA-Inhibition caused by discrete gene regions in a Down syndrome model","author":"Hannan","year":"2025","journal-title":"bioRxiv"},{"key":"B27","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/35012518","article-title":"The DNA sequence of human chromosome 21","volume":"405","author":"Hattori","year":"2000","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","first-page":"D884","DOI":"10.1093\/NAR\/GKAA942","article-title":"Ensembl 2021","volume":"49","author":"Howe","year":"2021","journal-title":"Nucleic Acids Research"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1016\/J.STEMCR.2018.02.001","article-title":"Modeling Down syndrome with patient iPSCs reveals cellular and migration deficits of GABAergic neurons","volume":"10","author":"Huo","year":"2018","journal-title":"Stem Cell Reports"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1038\/ejhg.2015.71","article-title":"DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies","volume":"23","author":"Ji","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/J.YDBIO.2025.06.009","article-title":"The role of goldilocks protein kinase DYRK1A in embryonic development","volume":"525","author":"Johnson","year":"2025","journal-title":"Dev. Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.ajhg.2021.12.015","article-title":"A transchromosomic rat model with human chromosome 21 shows robust Down syndrome features","volume":"109","author":"Kazuki","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/S41467-018-03190-3","article-title":"High-efficiency RNA-Based reprogramming of human primary fibroblasts","volume":"9","author":"Kogut","year":"2018","journal-title":"Nat. Commun."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1002\/AUR.2995","article-title":"Characterizing the autism spectrum phenotype in DYRK1A-related syndrome","volume":"16","author":"Kurtz-Nelson","year":"2023","journal-title":"Autism Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.devcel.2008.10.014","article-title":"The protein kinase DYRK1A regulates Caspase-9-Mediated apoptosis during retina development","volume":"15","author":"Laguna","year":"2008","journal-title":"Dev. Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2775","DOI":"10.1093\/HMG\/DDT125","article-title":"Triplication of DYRK1A causes retinal structural and functional alterations in Down syndrome","volume":"22","author":"Laguna","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e11614","DOI":"10.7554\/ELIFE.11614","article-title":"Genetic dissection of Down syndrome-associated congenital heart defects using a new mouse mapping panel","volume":"5","author":"Lana-Elola","year":"2016","journal-title":"eLife"},{"key":"B38","doi-asserted-by":"publisher","first-page":"dmm049157","DOI":"10.1242\/DMM.049157","article-title":"Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down syndrome-related phenotypes","volume":"14","author":"Lana-Elola","year":"2021","journal-title":"Dis. Models and Mechanisms"},{"key":"B39","doi-asserted-by":"publisher","first-page":"6883","DOI":"10.1126\/SCITRANSLMED.ADD6883","article-title":"Increased dosage of DYRK1A leads to congenital heart defects in a mouse model of Down syndrome","volume":"16","author":"Lana-Elola","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1554093","DOI":"10.3389\/FNINS.2025.1554093","article-title":"Clinical and molecular overlap between nucleotide excision repair (NER) disorders and DYRK1A haploinsufficiency syndrome","volume":"19","author":"Le May","year":"2025","journal-title":"Front. Neuroscience"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1093\/HMG\/DDP047","article-title":"DYRK1A interacts with the REST\/NRSF-SWI\/SNF chromatin remodelling complex to deregulate gene clusters involved in the neuronal phenotypic traits of Down syndrome","volume":"18","author":"Lepagnol-Bestel","year":"2009","journal-title":"Hum. Molecular Genetics"},{"key":"B42","doi-asserted-by":"publisher","first-page":"575","DOI":"10.3390\/BIOLOGY13080575","article-title":"Structural magnetic resonance imaging-based surface morphometry analysis of pediatric Down syndrome","volume":"13","author":"Levman","year":"2024","journal-title":"Biology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/J.STEM.2012.08.004","article-title":"Trisomy correction in Down syndrome induced pluripotent stem cells","volume":"11","author":"Li","year":"2012","journal-title":"Cell Stem Cell"},{"key":"B44","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1096\/FJ.07-104539","article-title":"Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome","volume":"22","author":"Liu","year":"2008","journal-title":"FASEB Journal Official Publication Fed. Am. Soc. Exp. Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"10755","DOI":"10.1074\/jbc.M110.174540","article-title":"REST regulates DYRK1A transcription in a negative feedback loop","volume":"286","author":"Lu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/S12881-016-0276-4","article-title":"Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature","volume":"17","author":"Luco","year":"2016","journal-title":"BMC Med. Genet."},{"key":"B47","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/EJHG.2008.214","article-title":"Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21","volume":"17","author":"Lyle","year":"2009","journal-title":"Eur. Journal Human Genetics EJHG"},{"key":"B48","doi-asserted-by":"publisher","first-page":"e1544","DOI":"10.1002\/MGG3.1544","article-title":"DYRK1A pathogenic variants in two patients with syndromic intellectual disability and a review of the literature","volume":"8","author":"Meissner","year":"2020","journal-title":"Mol. Genetics and Genomic Medicine"},{"key":"B49","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1080\/15384101.2019.1577525","article-title":"DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169","volume":"18","author":"Menon","year":"2019","journal-title":"Cell Cycle"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1016\/j.ajhg.2008.03.001","article-title":"Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly","volume":"82","author":"M\u00f8ller","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2077","DOI":"10.1002\/stem.1968","article-title":"Brief report: Isogenic induced pluripotent stem cell lines from an adult with mosaic Down syndrome model accelerated neuronal ageing and neurodegeneration","volume":"33","author":"Murray","year":"2015","journal-title":"STEM CELLS"},{"key":"B52","doi-asserted-by":"publisher","first-page":"104692","DOI":"10.1016\/j.ebiom.2023.104692","article-title":"Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels","volume":"94","author":"Murray","year":"2023","journal-title":"eBioMedicine"},{"key":"B53","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/J.EBIOM.2015.01.010","article-title":"DYRK1A-mediated cyclin D1 degradation in neural stem cells contributes to the neurogenic cortical defects in Down syndrome","volume":"2","author":"Najas","year":"2015","journal-title":"EBioMedicine"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1462893","DOI":"10.3389\/FNINS.2024.1462893","article-title":"Skeletal health in DYRK1A syndrome","volume":"18","author":"Otte","year":"2024","journal-title":"Front. Neuroscience"},{"key":"B55","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.stemcr.2018.05.004","article-title":"The impact of APP on alzheimer-like pathogenesis and gene expression in Down syndrome iPSC-Derived neurons","volume":"11","author":"Ovchinnikov","year":"2018","journal-title":"Stem Cell Rep."},{"key":"B56","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1002\/AJMG.A.32729","article-title":"The phenotype of persons having mosaicism for trisomy 21\/Down syndrome reflects the percentage of trisomic cells present in different tissues","author":"Papavassiliou","year":"2009","journal-title":"Am. J. Med. Genet. Part"},{"key":"B57","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/AJMG.A.36861","article-title":"Mosaicism for trisomy 21: a review","volume":"167","author":"Papavassiliou","year":"2015","journal-title":"Am. J. Med. Genet. Part A"},{"key":"B58","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/J.CELL.2008.07.041","article-title":"Disease-specific induced pluripotent stem cells","volume":"134","author":"Park","year":"2008","journal-title":"Cell"},{"key":"B59","doi-asserted-by":"publisher","first-page":"31895","DOI":"10.1074\/JBC.M110.147520","article-title":"Dyrk1A phosphorylates p53 and inhibits proliferation of embryonic neuronal cells","volume":"285","author":"Park","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B60","doi-asserted-by":"publisher","first-page":"e797","DOI":"10.1002\/MGG3.797","article-title":"Partial trisomy 21 map: ten cases further supporting the highly restricted Down syndrome critical region (HR\u2010DSCR) on human chromosome 21","volume":"7","author":"Pelleri","year":"2019","journal-title":"Mol. Genet. and Genomic Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1186\/S12920-022-01422-6","article-title":"Partial trisomy 21 with or without highly restricted Down syndrome critical region (HR-DSCR): report of two new cases and reanalysis of the genotype\u2013phenotype association","volume":"15","author":"Pelleri","year":"2022","journal-title":"BMC Med. Genomics"},{"key":"B62","doi-asserted-by":"publisher","first-page":"103917","DOI":"10.1016\/j.scr.2026.103917","article-title":"Generation of a human induced pluripotent stem cell line (FDIBSi002-A) derived from a patient with DYRK1A carrying a heterozygous DYRK1A mutation (c.1042G>A)","volume":"91","author":"Peng","year":"2026","journal-title":"Stem Cell Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"19912","DOI":"10.1038\/s41598-022-24284-5","article-title":"Impaired macroglial development and axonal conductivity contributes to the neuropathology of DYRK1A-related intellectual disability syndrome","volume":"12","author":"Pijuan","year":"2022","journal-title":"Sci. Rep."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1176\/APPI.AJP.158.10.1659","article-title":"Neuroanatomy of down\u2019s syndrome: a high-resolution MRI study","volume":"158","author":"Pinter","year":"2001","journal-title":"Am. J. Psychiatry"},{"key":"B65","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/s41419-026-08956-y","article-title":"Abnormal neuronal and synaptic morphology in Down syndrome brains reproduces in human isogenic cellular models","volume":"17","author":"Ple\u0107a\u0161","year":"2026","journal-title":"Cell Death and Dis."},{"key":"B66","doi-asserted-by":"publisher","first-page":"529","DOI":"10.3233\/JAD-130824","article-title":"Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) enhances tau expression","volume":"37","author":"Qian","year":"2013","journal-title":"J. Alzheimer\u2019s Disease JAD"},{"key":"B67","doi-asserted-by":"publisher","first-page":"104717","DOI":"10.1016\/J.XPRO.2026.104717","article-title":"A Researcher\u2019s guide to rodent models of Down syndrome: recent insights and translational perspectives","volume":"7","author":"Raza","year":"2026","journal-title":"Star. Protoc."},{"key":"B68","doi-asserted-by":"publisher","first-page":"dev201077","DOI":"10.1242\/dev.201077","article-title":"Craniofacial dysmorphology in Down syndrome is caused by increased dosage of Dyrk1a and at least three other genes","volume":"150","author":"Redhead","year":"2023","journal-title":"Available A. T."},{"key":"B69","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/NG1095-177","article-title":"A mouse model for Down syndrome exhibits learning and behaviour deficits","volume":"11","author":"Reeves","year":"1995","journal-title":"Nat. Genetics"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/S13244-019-0729-3","article-title":"Neuroimaging assessment in Down syndrome: a pictorial review","volume":"10","author":"Rodrigues","year":"2019","journal-title":"Insights Into Imaging"},{"key":"B71","doi-asserted-by":"publisher","first-page":"6014","DOI":"10.1038\/s41598-019-42445-x","article-title":"A comprehensive proteomics-based interaction screen that links DYRK1A to RNF169 and to the DNA damage response","volume":"9","author":"Roewenstrunk","year":"2019","journal-title":"Sci. Rep."},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1136\/BCR.05.2009.1914","article-title":"Familial 4.3 Mb duplication of 21q22 sheds new light on the Down syndrome critical region","volume":"2009","author":"Ronan","year":"2009","journal-title":"BMJ Case Reports"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1016\/J.CELREP.2018.04.008","article-title":"DYRK1A kinase positively regulates angiogenic responses in endothelial cells","volume":"23","author":"Rozen","year":"2018","journal-title":"Cell Rep."},{"key":"B74","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/S13039-018-0410-4","article-title":"Down syndrome phenotype in a boy with a mosaic microduplication of chromosome 21q22","volume":"11","author":"Schnabel","year":"2018","journal-title":"Mol. Cytogenetics"},{"key":"B75","doi-asserted-by":"publisher","first-page":"103831","DOI":"10.1016\/J.SCR.2025.103831","article-title":"Down syndrome (trisomy 21) disease-specific human embryonic stem cell (hESC) lines, UMICHe003-A\/UM152-1, UMICHe004-A\/UM202-1, and UMICHe005-A\/UM229-1","volume":"88","author":"Smith","year":"2025","journal-title":"Stem Cell Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/J.CELL.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"B77","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/J.CELL.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"B78","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/J.1742-4658.2010.07954","article-title":"MNB\/DYRK1A as a multiple regulator of neuronal development","volume":"278","author":"Tejedor","year":"2011","journal-title":"FEBS J."},{"key":"B79","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/0896-6273(95)90286-4","article-title":"Minibrain: a new protein kinase family involved in postembryonic neurogenesis in drosophila","volume":"14","author":"Tejedor","year":"1995","journal-title":"Neuron"},{"key":"B80","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/J.1399-0004.2010.01544.X","article-title":"Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly","volume":"79","author":"Van Bon","year":"2011","journal-title":"Clin. Genetics"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/j.celrep.2013.03.027","article-title":"The protein interaction landscape of the human CMGC kinase group","volume":"3","author":"Varjosalo","year":"2013","journal-title":"Cell Rep."},{"key":"B82","doi-asserted-by":"publisher","first-page":"23926","DOI":"10.1038\/s41598-024-74190-1","article-title":"Differential regulation of expression of the protein kinases DYRK1A and DYRK1B in cancer cells","volume":"14","author":"Vorwerk","year":"2024","journal-title":"Sci. Rep."},{"key":"B83","doi-asserted-by":"publisher","first-page":"9962","DOI":"10.1073\/PNAS.1216575110","article-title":"Deficits in human trisomy 21 iPSCs and neurons","volume":"110","author":"Weick","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B84","doi-asserted-by":"publisher","first-page":"dmm052740","DOI":"10.1242\/DMM.052740","article-title":"Leucettinib-21 decreases dosage effects of DYRK1A in human trisomy 21 induced pluripotent stem cell-derived neural cells","volume":"19","author":"West","year":"2026","journal-title":"Dis. Models and Mech."},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1242\/BIO.032862","article-title":"Functional characterization of DYRK1A missense variants associated with a syndromic form of intellectual deficiency and autism","volume":"7","author":"Widowati","year":"2018","journal-title":"Biol. Open"},{"key":"B86","doi-asserted-by":"publisher","first-page":"4004","DOI":"10.1523\/JNEUROSCI.4711-09.2010","article-title":"Dyrk1A overexpression inhibits proliferation and induces premature neuronal differentiation of neural progenitor cells","volume":"30","author":"Yabut","year":"2010","journal-title":"J. Neurosci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/S41598-017-00682-Y","article-title":"Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice","volume":"7","author":"Yin","year":"2017","journal-title":"Sci. Reports"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1126\/SCIENCE.1151526","article-title":"Induced pluripotent stem cell lines derived from human somatic cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"B89","doi-asserted-by":"publisher","first-page":"103155","DOI":"10.1016\/J.SCR.2023.103155","article-title":"Generation of an induced pluripotent stem cell line (NCHi010-A) from a 6-year-old female with Down syndrome and without congenital heart disease","volume":"71","author":"Yu","year":"2023","journal-title":"Stem Cell Res."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1963992\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:20:28Z","timestamp":1791357628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1963992\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":89,"alternative-id":["10.3389\/fcell.2026.1963992"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1963992","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"1963992"}}