Cited by 145Genomic variations and chromosomal abnormalitiesGenetics and Neurodevelopmental DisordersDown syndrome and intellectual disability research

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies

Open access

Ji, Jianling, Lee, Hane, Argiropoulos, Bob, Dorrani, Naghmeh, Mann, John, Martinez-Agosto, Julian A, Gomez-Ospina, Natalia, Gallant, Natalie, Bernstein, Jonathan A, Hudgins, Louanne, Slattery, Leah, Isidor, Bertrand, Le Caignec, Cédric, David, Albert, Obersztyn, Ewa, Wiśniowiecka-Kowalnik, Barbara, Fox, Michelle, Deignan, Joshua L, Vilain, Eric, Hendricks, Emily, Horton Harr, Margaret, Noon, Sarah E, Jackson, Jessi R, Wilkens, Alisha, Mirzaa, Ghayda, Salamon, Noriko, Abramson, Jeff, Zackai, Elaine H, Krantz, Ian, Innes, A Micheil, Nelson, Stanley F, Grody, Wayne W, Quintero-Rivera, Fabiola·2015·European Journal of Human Genetics

DOI 10.1038/ejhg.2015.71PMC PMC4613469

Open this paper in CoChat — free account

Abstract

Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from -2 SD to -5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype-phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs.

Integrity signals

Registry

Crossref · 10.1038/ejhg.2015.71

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
MolProbity : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165
Chromosomal microarray versus karyotyping for prenatal diagnosis
Wapner, R. J., Martin, C. L., Levy, B., Ballif, B. C., Eng, C. M., Zachary, J. M., Savage, M., Platt, L. D., Saltzman, D., Grobman, W. A., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1203382 · Cited by 1,412
Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders
Lee, H., Deignan, J. L., Dorrani, N., Strom, S. P., Kantarci, S., Quintero‐Rivera, F., Das, K., Toy, T. L., Harry, B., Yourshaw, M., et al. (2014) · JAMA · doi:10.1001/jama.2014.14604 · Cited by 991
Self-citation
The Structural Basis for Control of Eukaryotic Protein Kinases
Endicott, J., Noble, M. E. M., & Johnson, L. N. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052410-090317 · Cited by 440
minibrain: A new protein kinase family involved in postembryonic neurogenesis in Drosophila
Tejedor, F. J., Zhu, X., Kaltenbach, E., Ackermann, A., Baumann, A., Canal, I., Heisenberg, M., Fischbach, K. F., & Pongs, O. (1995) · Neuron · doi:10.1016/0896-6273(95)90286-4 · Cited by 379
Dyrk1A Haploinsufficiency Affects Viability and Causes Developmental Delay and Abnormal Brain Morphology in Mice
Fotaki, V., Dierssen, M., Alcántara, S., Martínez, S., Martí, E., Casas, C., Visa, J., Soriano, E., Estivill, X., & Arbonés, M. L. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.18.6636-6647.2002 · Cited by 344
Activation-Loop Autophosphorylation Is Mediated by a Novel Transitional Intermediate Form of DYRKs
Lochhead, P. A., Sibbet, G. J., MORRICE, N. A., & Cleghon, V. (2005) · Cell · doi:10.1016/j.cell.2005.03.034 · Cited by 330
DYRK family of protein kinases: evolutionary relationships, biochemical properties, and functional roles
Aranda, S., Laguna, A., & de la Luna, S. (2011) · The FASEB Journal · doi:10.1096/fj.10-165837 · Cited by 320

Flagged first, then by citations

Show all 46 references

Sorted by citations

Advancing the understanding of autism disease mechanisms through genetics
de la Torre-Ubieta, L., Won, H., Stein, J. L., & Geschwind, D. H. (2016) · Nature Medicine · doi:10.1038/nm.4071 · Cited by 827
Autism genetics: opportunities and challenges for clinical translation
Vorstman, J. A. S., Parr, J. R., Moreno‐De‐Luca, D., Anney, R., Nürnberger, J. I., & Hallmayer, J. F. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.4 · Cited by 517
Down syndrome and the complexity of genome dosage imbalance
Antonarakis, S. E. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.154 · Cited by 314
Optical genome mapping enables constitutional chromosomal aberration detection
Mantere, T., Neveling, K., Pebrel‐Richard, C., Benoist, M., van de Zande, G., Kater‐Baats, E., Baatout, I., van Beek, R., Yammine, T., Oorsprong, M., et al. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.05.012 · Cited by 256
Genomics, convergent neuroscience and progress in understanding autism spectrum disorder
Willsey, H. R., Willsey, A. J., Wang, B., & State, M. W. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00576-7 · Cited by 239
DYRK1A and cognition: A lifelong relationship
Arbonés, M. L., Thomazeau, A., Nakano-Kobayashi, A., Hagiwara, M., & Delabar, J. M. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.09.010 · Cited by 174
Syndromic autism spectrum disorders: moving from a clinically defined to a molecularly defined approach
Fernandez, B. A., & Scherer, S. W. (2017) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2017.19.4/sscherer · Cited by 169
Cellular phenotypes in human iPSC-derived neurons from a genetic model of autism spectrum disorder
Deshpande, A., Yadav, S., Dao, D. Q., Wu, Z.-Y., Hokanson, K. C., Cahill, M. K., Wiita, A. P., Jan, Y.-N., Ullian, E. M., & Weiss, L. A. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.037 · Cited by 151
Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview
Lindberg, M. F., & Meijer, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116047 · Cited by 126
Mutations and Modeling of the Chromatin Remodeler CHD8 Define an Emerging Autism Etiology
Barnard, R., Pomaville, M. B., & O’Roak, B. J. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00477 · Cited by 111
Cockayne’s Syndrome A and B Proteins Regulate Transcription Arrest after Genotoxic Stress by Promoting ATF3 Degradation
Epanchintsev, A., Costanzo, F., Rauschendorf, M., Caputo, M., Ye, T., Donnio, L., Proietti‐De‐Santis, L., Coin, F., Laugel, V., & Egly, J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.11.009 · Cited by 104
Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience
Willsey, H. R., Exner, C. R. T., Xu, Y., Everitt, A., Sun, N., Wang, B., Dea, J., Schmunk, G., Zaltsman, Y., Teerikorpi, N., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.01.002 · Cited by 98
Application of CRISPR/Cas9 to human-induced pluripotent stem cells: from gene editing to drug discovery
Masi, C. D., Spitalieri, P., Murdocca, M., Novelli, G., & Sangiuolo, F. C. (2020) · Human Genomics · doi:10.1186/s40246-020-00276-2 · Cited by 108
DYRK1A: a down syndrome-related dual protein kinase with a versatile role in tumorigenesis
Laham, A. J., Saber-Ayad, M. M., & El‐Awady, R. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03626-4 · Cited by 95
Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome
Catuara‐Solarz, S., Espinosa‐Carrasco, J., Erb, I., Langohr, K., González, J. R., Notredame, C., & Dierssen, M. (2016) · eNeuro · doi:10.1523/eneuro.0103-16.2016 · Cited by 90
Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development
Dang, T., Duan, W. Y., Yu, B., Tong, D. L., Cheng, C., Zhang, Y. F., Wu, W., Ye, K., Zhang, W. X., Wu, M., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.253 · Cited by 80
DYRK1A Protein, A Promising Therapeutic Target to Improve Cognitive Deficits in Down Syndrome
Féki, A., & Hibaoui, Y. (2018) · Brain Sciences · doi:10.3390/brainsci8100187 · Cited by 71
Clinical phenotype of ASD-associated DYRK1A haploinsufficiency
Earl, R. K., Turner, T. N., Mefford, H. C., Hudac, C. M., Gerdts, J. A., Eichler, E. E., & Bernier, R. (2017) · Molecular Autism · doi:10.1186/s13229-017-0173-5 · Cited by 75
The chromosome 21 kinase DYRK1A: emerging roles in cancer biology and potential as a therapeutic target
Rammohan, M., Harris, E., Bhansali, R. S., Zhao, E., Li, L. S., & Crispino, J. D. (2022) · Oncogene · doi:10.1038/s41388-022-02245-6 · Cited by 68
Overexpression ofDyrk1A, a Down Syndrome Candidate, Decreases Excitability and Impairs Gamma Oscillations in the Prefrontal Cortex
Ruiz-Mejías, M., de Lagrán, M. M., Mattia, M., Castano-Prat, P., Perez-Mendez, L., Ciria‐Suarez, L., Gener, T., Sancristóbal, B., García‐Ojalvo, J., Gruart, A., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2517-15.2016 · Cited by 64
Recurrent reciprocal copy number variants: Roles and rules in neurodevelopmental disorders
Deshpande, A., & Weiss, L. A. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22587 · Cited by 61
DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169
Menon, V., Ananthapadmanabhan, V., Swanson, S. K., Saini, S., Sesay, F. F., Yakovlev, V. A., Florens, L. A., DeCaprio, J. A., Washburn, M. P., Dozmorov, M. G., et al. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1577525 · Cited by 61
DYRK1A-haploinsufficiency in mice causes autistic-like features and febrile seizures
Raveau, M., Shimohata, A., Amano, K., Miyamoto, H., & Yamakawa, K. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.12.003 · Cited by 53
Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature
Luco, S. M., Pohl, D., Sell, E., Wagner, J. D., Dyment, D. A., & Daoud, H. (2016) · BMC Medical Genetics · doi:10.1186/s12881-016-0276-4 · Cited by 52
Precisely controlling endogenous protein dosage in hPSCs and derivatives to model FOXG1 syndrome
Zhu, W., Zhang, B., Li, M., Mo, F., Mi, T., Wu, Y., Teng, Z., Zhou, Q., Li, W., & Hu, B. (2019) · Nature Communications · doi:10.1038/s41467-019-08841-7 · Cited by 46
Dyrk1a gene dosage in glutamatergic neurons has key effects in cognitive deficits observed in mouse models of MRD7 and Down syndrome
Brault, V., Nguyen, T. L., Gutiérrez, J. F., Iacono, G., Birling, M., Lalanne, V., Méziane, H., Manousopoulou, A., Pavlovic, G., Lindner, L., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009777 · Cited by 43
Function and inhibition of DYRK1A: Emerging roles of treating multiple human diseases
Yang, Y., Fan, X., Liu, Y., Ye, D., Liu, C., Yang, H., Su, Z., Zhang, Y., & Liu, Y. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115521 · Cited by 43
Impaired development of neocortical circuits contributes to the neurological alterations in DYRK1A haploinsufficiency syndrome
Arranz, J., Balducci, E., Arató, K., Sánchez‐Elexpuru, G., Najas, S., Parras, A., Rebollo, E., Pijuan, I., Erb, I., Verde, G., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.02.022 · Cited by 43
Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability
Lee, J. S., Hwang, H. Y., Kim, S. Y., Kim, K. J., Choi, J. S., Woo, M. J., Choi, Y. M., Jun, J. K., Lim, B. C., & Chae, J. (2018) · Annals of Laboratory Medicine · doi:10.3343/alm.2018.38.5.473 · Cited by 42
Neurodevelopmental disorder risk gene DYRK1A is required for ciliogenesis and brain size in Xenopus embryos
Willsey, H. R., Xu, Y., Everitt, A., Dea, J., Exner, C. R. T., Willsey, A. J., State, M. W., & Harland, R. M. (2020) · Development · doi:10.1242/dev.189290 · Cited by 42
Dyrk1a Mutations Cause Undergrowth of Cortical Pyramidal Neurons via Dysregulated Growth Factor Signaling
Levy, J., LaFlamme, C. W., Tsaprailis, G., Crynen, G. C., & Page, D. T. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.01.012 · Cited by 42
Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder
Courraud, J., Chater‐Diehl, E., Durand, B., Vincent, M., Moreno, M. D. M. M., Boujelbene, I., Drouot, N., Genschik, L., Schaefer, É., Nizon, M., et al. (2021) · Genetics in Medicine · doi:10.1038/s41436-021-01263-1 · Cited by 37
Self-citation
High diagnostic yield of clinically unidentifiable syndromic growth disorders by targeted exome sequencing
Kim, Y., Lee, Y.-J., Park, J., Lee, H., Chong, K.-C.-O., Kim, S.-Y., Hwang, J., Jang, J., & Yoo, H. (2017) · Clinical Genetics · doi:10.1111/cge.13038 · Cited by 35
Self-citation
Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
Starbuck, J. M., Llambrich, S., González, R., Albaigès, J., Sarlé, A., Wouters, J., González, A., Sevillano, X., Sharpe, J. A., de la Torre, R., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-83757-1 · Cited by 34
Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery
Walter, C., Marada, A., Suhm, T., Ernsberger, R., Muders, V., Küçükköse, C., Sánchez‐Martín, P., Hu, Z., Aich, A., Loroch, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24426-9 · Cited by 36
Genotype–phenotype correlations and novel molecular insights into the DHX30-associated neurodevelopmental disorders
Mannucci, I., Dang, N. D.-P., Huber, H., Murry, J. B., Abramson, J., Althoff, T., Banka, S., Baynam, G. S., Bearden, D., Beleza‐Meireles, A., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00900-3 · Cited by 33
Self-citation
DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract
Blackburn, A. T. M., Bekheirnia, N., Uma, V. C., Corkins, M. E., Xu, Y., Rosenfeld, J. A., Bainbridge, M. N., Yang, Y., Liu, P., Madan‐Khetarpal, S., et al. (2019) · Genetics in Medicine · doi:10.1038/s41436-019-0576-0 · Cited by 34
Self-citation
Heterozygous variants inACTL6A, encoding a component of the BAF complex, are associated with intellectual disability
Marom, R., Jain, M., Burrage, L. C., Song, I.-W., Graham, B. H., Brown, C., Stevens, S. J. C., Stegmann, A. P. A., Gunter, A. T., Kaplan, J. D., et al. (2017) · Human Mutation · doi:10.1002/humu.23282 · Cited by 33
Kinase Signaling in Dendritic Development and Disease
Nourbakhsh, K., & Yadav, S. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.624648 · Cited by 31
Aristolactam BIII, a naturally derived DYRK1A inhibitor, rescues Down syndrome-related phenotypes
Choi, M., Kim, A., Ham, Y., Lee, J., Kim, D., Yang, A., Jo, M. J., Yoon, E., Heo, J., Han, S., et al. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153695 · Cited by 34
DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner
Strine, M. S., Cai, W. L., Wei, J., Alfajaro, M. M., Filler, R. B., Biering, S. B., Sarnik, S. A., Chow, R. D.-W., Patil, A., Cervantes, K. S., et al. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3002097 · Cited by 29
Inhibition of DYRK1A disrupts neural lineage specificationin human pluripotent stem cells
Bellmaine, S. F., Ovchinnikov, D. A., Manallack, D. T., Cuddy, C., Elefanty, A. G., Stanley, E. G., Wolvetang, E. J., Williams, S. J., & Pera, M. F. (2017) · eLife · doi:10.7554/elife.24502 · Cited by 30
Functional characterization of DYRK1A missense variants associated with a syndromic form of intellectual deficiency and autism
Widowati, E. W., Ernst, S., Hausmann, R., Müller‐Newen, G., & Becker, W. B. (2018) · Biology Open · doi:10.1242/bio.032862 · Cited by 30
Structural analysis of pathogenic mutations in theDYRK1Agene in patients with developmental disorders
Evers, J. M. G., Laskowski, R. A., Bértoli, M., Clayton‐Smith, J., Deshpande, C., Eason, J., Elmslie, F., Flinter, F. A., Gardiner, C. A., Hurst, J. A., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw409 · Cited by 33
DYRK1A Kinase Inhibitors Promote β-Cell Survival and Insulin Homeostasis
Barzowska, A., Pucelik, B., Pustelny, K., Matsuda, A., Martyniak, A., Stępniewski, J., Maksymiuk, A., Dawidowski, M., Rothweiler, U., Dulak, J., et al. (2021) · Cells · doi:10.3390/cells10092263 · Cited by 27
Human cytomegalovirus (CMV) dysregulates neurodevelopmental pathways in cerebral organoids
Egilmezer, E., Hamilton, S. T., Foster, C. S. P., Marschall, M., & Rawlinson, W. D. (2024) · Communications Biology · doi:10.1038/s42003-024-05923-1 · Cited by 32
Next generation cytogenetics: genome-imaging enables comprehensive structural variant detection for 100 constitutional chromosomal aberrations in 85 samplesPreprint
Mantere, T., Neveling, K., Pebrel‐Richard, C., Benoist, M., van de Zande, G., Kater‐Baats, E., Baatout, I., van Beek, R., Yammine, T., Oorsprong, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.15.205245 · Cited by 24
The language-ready head: Evolutionary considerations
Boeckx, C. (2017) · Psychonomic Bulletin & Review · doi:10.3758/s13423-016-1087-5 · Cited by 23
Insights from the protein interaction Universe of the multifunctional “Goldilocks” kinase DYRK1A
Ananthapadmanabhan, V., Shows, K. H., DICKINSON, A. J. G., & Litovchick, L. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1277537 · Cited by 23
Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders
Mozzi, A., Forni, D., Cagliani, R., Pozzoli, U., Clerici, M., & Sironi, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-06440-4 · Cited by 19
DYRK1A Regulates the Bidirectional Axonal Transport of APP in Human-Derived Neurons
Fernandez Bessone, I., Navarro, J., Martinez, E., Karmirian, K., Holubiec, M., Alloatti, M., Goto-Silva, L., Arnaiz Yepez, C., Martins-de-Souza, D., Minardi Nascimento, J., et al. (2022) · The Journal of Neuroscience · doi:10.1523/jneurosci.2551-21.2022 · Cited by 21
Understanding the genetic mechanisms and cognitive impairments in Down syndrome: towards a holistic approach
Abukhaled, Y., Hatab, K., Awadhalla, M., & Hamdan, H. (2023) · Journal of Neurology · doi:10.1007/s00415-023-11890-0 · Cited by 30
Modeling Down syndrome in cells: From stem cells to organoids
Gough, G., O’Brien, N. L., Alić, I., Goh, P. A., Yeap, Y. J., Groet, J., Nižetić, D., & Murray, A. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.10.003 · Cited by 21
A novel de novo heterozygous DYRK1A mutation causes complete loss of DYRK1A function and developmental delay
Lee, K., Choi, M., Kwon, D.-W., Kim, D., Choi, J.-M., Kim, A., Ham, Y., Han, S., Cho, S., & Cheon, C. K. (2020) · Scientific Reports · doi:10.1038/s41598-020-66750-y · Cited by 20
Social motivation a relative strength in DYRK1A syndrome on a background of significant speech and language impairments
Morison, L. D., Braden, R. O., Amor, D. J., Brignell, A., van Bon, B. W. M., & Morgan, A. T. (2022) · European Journal of Human Genetics · doi:10.1038/s41431-022-01079-w · Cited by 20
DYRK1A signalling synchronizes the mitochondrial import pathways for metabolic rewiring
Marada, A., Walter, C., Suhm, T., Shankar, S., Nandy, A., Brummer, T., Dhaouadi, I., Vögtle, F. ‐., & Meisinger, C. (2024) · Nature Communications · doi:10.1038/s41467-024-49611-4 · Cited by 19
Ocular Phenotype Associated with DYRK1A Variants
Méjécase, C., Way, C., Owen, N., & Moosajee, M. (2021) · Genes · doi:10.3390/genes12020234 · Cited by 19
Genome-wide miRNA profiling in plasma of pregnant women with down syndrome fetuses
Zednikova, I., Chylíková, B., Šeda, O., Korabečná, M., Pazourková, E., Brestak, M., Krkavcová, M., Calda, P., & Hořínek, A. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-05545-w · Cited by 18
Functions of SRPK , CLK and DYRK kinases in stem cells, development, and human developmental disorders
Hogg, E. K. J., & Findlay, G. M. (2023) · FEBS Letters · doi:10.1002/1873-3468.14723 · Cited by 18
Down syndrome phenotype in a boy with a mosaic microduplication of chromosome 21q22
Schnabel, F., Smogavec, M., Funke, R., Pauli, S., Burfeind, P., & Bartels, I. (2018) · Molecular Cytogenetics · doi:10.1186/s13039-018-0410-4 · Cited by 17
Neurocognitive and neurobehavioral characterization of two frequent forms of neurodevelopmental disorders: the DYRK1A and the Wiedemann–Steiner syndromes
Durand, B., Schaefer, É., Burger, P., Baer, S., Schroder, C. M., Mandel, J., Piton, A., & Coutelle, R. (2022) · Clinical Genetics · doi:10.1111/cge.14190 · Cited by 16
Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans
Mack, H. I. D., Kremer, J., Albertini, E., Mack, E., & Jansen‐Dürr, P. (2022) · BMC Genomics · doi:10.1186/s12864-021-08176-y · Cited by 14
Pathogenic mutation hotspots in protein kinase domain structure
Medvedev, K. E., Schaeffer, R. D., Pei, J., & Grishin, N. V. (2023) · Protein Science · doi:10.1002/pro.4750 · Cited by 12
A De Novo Mutation in DYRK1A Causes Syndromic Intellectual Disability: A Chinese Case Report
Qiao, F., Shao, B., Wang, C., Wang, Y., Zhou, R., Liu, G., Meng, L., Hu, P., & Xu, Z. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.01194 · Cited by 13
Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly
Sokol, D. K., & Lahiri, D. K. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1201723 · Cited by 11
Lithium normalizes ASD-related neuronal, synaptic, and behavioral phenotypes in DYRK1A-knockin mice
Roh, J. D., Bae, M. H., Kim, H., Yang, Y., Lee, Y., Cho, Y., Lee, S., Li, Y., Yang, E., Jang, H., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02865-2 · Cited by 11
Impaired macroglial development and axonal conductivity contributes to the neuropathology of DYRK1A-related intellectual disability syndrome
Pijuan, I., Balducci, E., Soto‐Sánchez, C., Fernández, E., Barallobre, M. J., & Arbonés, M. L. (2022) · Scientific Reports · doi:10.1038/s41598-022-24284-5 · Cited by 11
IDGenetics: a comprehensive database for genes and mutations of intellectual disability related disorders
Chen, C., Chen, D., Xue, H., Liu, X., Zhang, T., Tang, S., Li, W., & Xu, X. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.08.027 · Cited by 11
Characterization of phenotypic range in DYRK1A haploinsufficiency syndrome using standardized behavioral measures
Fenster, R., Ziegler, A. C., Kentros, C., Geltzeiler, A., Snyder, L. G., Brooks, E. A., & Chung, W. K. (2022) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62721 · Cited by 11
Dyrk1a is required for craniofacial development in Xenopus laevis.
Johnson, H. K., Wahl, S., Sesay, F. F., Litovchick, L., & DICKINSON, A. J. G. (2024) · Developmental Biology · doi:10.1016/j.ydbio.2024.04.004 · Cited by 10
Abnormalities of DYRK1A-Cytoskeleton Complexes in the Blood Cells as Potential Biomarkers of Alzheimer’s Disease
Dowjat, K., Adayev, T., Wojda, U., Brzozowska, K., Barczak, A. K., Gabryelewicz, T., & Hwang, Y. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190475 · Cited by 10
Design, synthesis, and biological evaluation of β-carboline-cinnamic acid derivatives as DYRK1A inhibitors in the treatment of diabetes
Guan, L., Li, A., Song, P., Su, W., Zhang, S., Chen, J., Jiao, X., & Li, W. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107676 · Cited by 9
Sex-specific trisomic Dyrk1a-related skeletal phenotypes during development in a Down syndrome model
LaCombe, J., Sloan, K., Thomas, J. R., Blackwell, M. P., Crawford, I., Bishop, F., Wallace, J. M., & Roper, R. J. (2024) · Disease Models & Mechanisms · doi:10.1242/dmm.050914 · Cited by 12
Zika virus: An emerging challenge for obstetrics and gynecology
Lin, J.-J., Chin, T., Chen, C., Chan, H., & Wu, T. (2017) · Taiwanese Journal of Obstetrics and Gynecology · doi:10.1016/j.tjog.2017.08.003 · Cited by 9
Comparison of Tranexamic acid, Remifentanil, and Hydralazine on the bleeding volume during Dacryocystorhinostomy surgery.
Farsani, D. M., Shetabi, H., Zadeh, A. R., & Rad, N. S. (2022) · PubMed Central · Cited by 9
Brain white matter abnormalities associated with copy number variants
Vigdorovich, N., Ben‐Sira, L., Blumkin, L., Precel, R., Nezer, I., Yosovich, K., Cross, Z., Vanderver, A. L., Lev, D., Lerman‐Sagie, T., et al. (2019) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61389 · Cited by 7
A rigorous in silico genomic interrogation at 1p13.3 reveals 16 autosomal dominant candidate genes in syndromic neurodevelopmental disorders
Ben‐Mahmoud, A., Jun, K. R., Gupta, V. R., Shastri, P., de la Fuente, A., Park, Y., Shin, K. C., Kim, C. A., da Cruz, A. D., Pinto, I. P., et al. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.979061 · Cited by 7
Skeletal health in DYRK1A syndrome
Otte, E. D., & Roper, R. J. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1462893 · Cited by 6
Whole-Exome Sequencing Identified a Novel DYRK1A Variant in a Patient With Intellectual Developmental Disorder, Autosomal Dominant 7
Obara, K., Abe, E., & Toyoshima, I. (2023) · Cureus · doi:10.7759/cureus.33379 · Cited by 6
Investigation of copy number variations on chromosome 21 detected by comparative genomic hybridization (CGH) microarray in patients with congenital anomalies
Li, W., Wang, X., & Li, S. (2018) · Molecular Cytogenetics · doi:10.1186/s13039-018-0391-3 · Cited by 6
The Role of Goldilocks Protein Kinase DYRK1A in Embryonic Development
Johnson, H. K., Litovchick, L., & DICKINSON, A. J. G. (2025) · Developmental Biology · doi:10.1016/j.ydbio.2025.06.009 · Cited by 5
Caregiver‐reported dental manifestations in individuals with genetic neurodevelopmental disorders
Ming, N. R., Noble, D., Chussid, S., Ziegler, A. C., & Chung, W. K. (2023) · International Journal of Paediatric Dentistry · doi:10.1111/ipd.13116 · Cited by 4
Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome
Moreau, M., Dard, R., Madani, A., Kandiah, J., Kassis, N., Ziga, J., Castiglione, H., Day, S., Bourgeois, T., Matrot, B., et al. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05245-9 · Cited by 4
Human Cytomegalovirus Dysregulates Cellular Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases and Sonic Hedgehog Pathway Proteins in Neural Astrocyte and Placental Models
Egilmezer, E., Hamilton, S. T., Lauw, G., Follett, J. E. L., Sonntag, E., Schütz, M., Marschall, M., & Rawlinson, W. D. (2024) · Viruses · doi:10.3390/v16060918 · Cited by 4
Case report: A novel de novo deletion mutation of DYRK1A is associated with intellectual developmental disorder, autosomal dominant 7
Zhou, C., Zhu, H., Xiang, Q., Mai, J., Wang, X., Wang, J., & Liu, S. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1174925 · Cited by 4
Ocular findings of albinism in DYRK1A-related intellectual disability syndrome
Ernst, J., Alabek, M. L., Eldib, A. A., Madan‐Khetarpal, S., Sebastian, J., Bhatia, A., Liasis, A. C., & Nischal, K. K. (2020) · Ophthalmic Genetics · doi:10.1080/13816810.2020.1814349 · Cited by 4
Sex specific emergence of trisomic Dyrk1a -related skeletal phenotypes in the development of a Down syndrome mouse modelPreprint
LaCombe, J., Sloan, K., Thomas, J. R., Blackwell, M. P., Crawford, I., Wallace, J. M., & Roper, R. J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.24.595804 · Cited by 4
Leucettinib-21 decreases dosage effects of DYRK1A in human trisomy 21 induced pluripotent stem cell-derived neural cells
West, N. R., Lindberg, M. F., Dairou, J., MacGregor, S., Puthireddy, S., Meijer, L., & Bhattacharyya, A. (2026) · Disease Models & Mechanisms · doi:10.1242/dmm.052740 · Cited by 3
Clinical course of epilepsy and white matter abnormality linked to a novel DYRK1A variant
Okazaki, T., Yamada, H., Matsuura, K., Kasagi, N., Miyake, N., Matsumoto, N., Adachi, K., Nanba, E., & Maegaki, Y. (2021) · Human Genome Variation · doi:10.1038/s41439-021-00157-7 · Cited by 3
An etiological study of intellectually disabled children under 14 years old in Anhui Province, China.
Li, S., & Tong, G. (2021) · PubMed Central · Cited by 3
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)
Ge, Y., Yan, C., Yin, T., Xingsheng, P., Xiong, Z., Wu, B., Wang, H., Xiong, M., & Zhou, W. (2024) · Stem Cell Research · doi:10.1016/j.scr.2024.103345 · Cited by 2
Discovery of a Novel DYRK1A Mutation (c.524del) in Intellectual Development Disorder Autosomal Dominant 7 (MRD7): A Comprehensive Case Analysis
Whitaker, F., & Serrano, A. (2024) · Case Reports in Genetics · doi:10.1155/2024/2926555 · Cited by 2
Interneuron migration defects during corticogenesis contribute to Dyrk1a haploinsufficiency syndrome pathogenesis
Hinckelmann, M.-V., Dubos, A., Artot, V., Rudolf, G., Nguyen, T. L., Tilly, P., Nalesso, V., Moreno, M. D. M. M., Birling, M., Godin, J. D., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03109-7 · Cited by 4
Two remarkable cases of haploinsufficiency found in the DYRK1A gene
Taşdelen, E., Tekbaş, U. C., Baş, H., & Sezer, A. (2024) · Acta Neurologica Belgica · doi:10.1007/s13760-024-02685-9 · Cited by 2
Rest Induces a Distinct Transcriptional Program in the Nervous System of the Exercised L. stagnalis
Rozenberg, J. M., Boguslavsky, D., Chistopolsky, I. A., Zakharov, I., & Dyakonova, V. E. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26146970 · Cited by 2
Interneuron migration defects during corticogenesis contribute to Dyrk1a haploinsufficiency syndrome pathogenesis via actomyosin dynamics deregulationsPreprint
Hinckelmann, M.-V., Dubos, A., Artot, V., Rudolf, G., Nguyen, T. L., Tilly, P., Nalesso, V., Moreno, M. D. M. M., Birling, M., Godin, J. D., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.09.566424 · Cited by 2
Early Human Postnatal Brain Development Through the Lens of Rare Genetic Disorders
Morrow, E. M. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.07.001 · Cited by 1
Case Report: Gut and spleen anomalies associated with DYRK1A syndrome
Infantino, I., Tocchioni, F., Ghionzoli, M., Coletta, R., Morini, F., & Morabito, A. (2023) · Frontiers in Pediatrics · doi:10.3389/fped.2022.936732 · Cited by 1
Rock around DYRK1A: Ethnic diversity, clinical challenges
Moroni, A., Pezzani, L., Alfei, E., Scatigno, A., Cereda, A., Marzaroli, M., Guuva, C., Gabbiadini, S., Pezzoli, L., Marchetti, D., et al. (2023) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.63140 · Cited by 1
A Rare Cause of Intellectual Disability
Oliveira, Í., Fernandes, A. S., Pereira, M. J., Rodrigues, M. T., Silva, N., & Mendonça, C. (2024) · Cureus · doi:10.7759/cureus.51451 · Cited by 1

Authors: Ji, J., Lee, H., Argiropoulos, B., Dorrani, N., Mann, J., Martinez-Agosto, J. A., Gomez-Ospina, N., Gallant, N., Bernstein, J. A., Hudgins, L., Slattery, L., Isidor, B., Le Caignec, C., David, A., Obersztyn, E., Wiśniowiecka-Kowalnik, B., Fox, M., Deignan, J. L., Vilain, E., Hendricks, E., Horton Harr, M., Noon, S. E., Jackson, J. R., Wilkens, A., Mirzaa, G., Salamon, N., Abramson, J., Zackai, E. H., Krantz, I., Innes, A. M., Nelson, S. F., Grody, W. W., & Quintero-Rivera, F.
Affiliations: University of California, Los Angeles (US)
University of Calgary (CA)
Kaiser Permanente (US)
Stanford Medicine (US)
Inserm (FR)
Instytut Matki i Dziecka (PL)
Seattle Children's Research Institute (US)
Children's Hospital of Philadelphia (US)
Tata Institute of Fundamental Research (IN)
ORCID: Ji, Jianling
Lee, Hane
Argiropoulos, Bob
Bernstein, Jonathan A
Hudgins, Louanne
Isidor, Bertrand
Obersztyn, Ewa
Deignan, Joshua L
Vilain, Eric
Hendricks, Emily
Mirzaa, Ghayda
Salamon, Noriko
Abramson, Jeff
Zackai, Elaine H
Krantz, Ian
Innes, A Micheil
Nelson, Stanley F
Venue: European Journal of Human Genetics
Publisher: Springer Science and Business Media LLC
Published: 2015-05-06
Volume: 23
Issue: 11
Pages: 1473-1481
ISSN: 1018-4813 (ISSN-L)
1476-5438
DOI: 10.1038/ejhg.2015.71
PMC: PMC4613469
OpenAlex: W1520236834
Cited by: 145
References: 46
Citations by year: 2026: 14 · 2025: 8 · 2024: 20 · 2023: 19 · 2022: 12 · 2021: 25 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 13 · 2016: 7 · 2015: 1
FWCI: 6.61
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: European Journal of Human Genetics (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institute of General Medical Sciences (GM078844, R01GM078844)
National Institute of Neurological Disorders and Stroke (K08NS092898)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
Keywords: DYRK1A, haploinsufficiency, Down syndrome critical region, microcephaly, intellectual disability, speech disorders, facial dysmorphism, genotype-phenotype correlation, de novo mutations, seizures, developmental delay, short stature
MeSH terms: Abnormalities, Multiple, Dyrk Kinases, Chromosome Deletion, Down Syndrome, Female, Humans, Male, Intellectual Disability, Microcephaly, Phenotype, Protein-Tyrosine Kinases, Protein Serine-Threonine Kinases, Facies, Polymorphism, Single Nucleotide, Haploinsufficiency

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks