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DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies
Open accessAbstract
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.
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“Mutations in DYRK1A and TCF4 cause syndromic diseases presenting with microcephaly and intellectual disability97–105.”
From Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders (2017) · cites this paper as [101]
In the citing paper
“For both genes haploinsufficiency is often associated with disease, indicating that adequate expression levels of these proteins are essential for neurodevelopment98, 101, 106.”
From Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders (2017) · cites this paper as [101]
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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
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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
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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
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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
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
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Lochhead, P. A., Sibbet, G. J., MORRICE, N. A., & Cleghon, V. (2005) · Cell · doi:10.1016/j.cell.2005.03.034 · Cited by 330
Aranda, S., Laguna, A., & de la Luna, S. (2011) · The FASEB Journal · doi:10.1096/fj.10-165837 · Cited by 320
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Lin, S., Hay, E., Thompson, D., Moosajee, M., Webster, A. R., Mahroo, O. A., Henderson, R., & Arno, G. (2025) · Ophthalmic Genetics · doi:10.1080/13816810.2025.2503388 · Cited by 1
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Massaroni, V., Donne, V. D., Arcangeli, V., Moriconi, F., & Chieffo, D. P. R. (2026) · Journal of Neurolinguistics · doi:10.1016/j.jneuroling.2026.101314 · Cited by 1
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Lanvin, P., Goronflot, T., Isidor, B., Nizon, M., Durand, B., Chehadeh, S. E., Geneviève, D., Ruault, V., Fradin, M., Pasquier, L., et al. (2023) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.63412 · Cited by 1
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Llambrich, S., Tielemans, B., Saliën, E., Atzori, M., Wouters, K., Bulck, V. V., Platt, M., Vanherp, L., Fernandez, N. G., de la Fuente, L. G., et al. (2023) · eLife · doi:10.1101/2023.07.31.551282 · Cited by 6
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Hammond, S. (2020) · Journal of International Crisis and Risk Communication Research
Pijuan, I., Balducci, E., Soto‐Sánchez, C., Fernández, E., Barallobre, M. J., & Arbonés, M. L. (2022) · Research Square · doi:10.21203/rs.3.rs-1925334/v1
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Llambrich, S., Tielemans, B., Saliën, E., Atzori, M., Wouters, K., Bulck, V. V., Platt, M., Vanherp, L., Fernandez, N. G., de la Fuente, L. G., et al. (2023) · eLife · doi:10.7554/elife.89763.1
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Nord, C., Tandon, A., Makiou, A., Leinonen, H., Wilson, S. I., Carlsson, L., & Jones, I. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.15.710015
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Costanzo, F. (2017) · theses.fr (ABES) · doi:10.70675/64c5c64bza3c5z49ffzbcb7z49be745e72fd
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Saavedra, J. T. A. (2024) · theses.fr (ABES) · doi:10.70675/064b45abz323ez478ez93ddz8ce0747170c2
Al-Younis, I. M., Basque, L., Crapoulet, N., Dyack, S., del Caño‐Ochoa, F., Ramón‐Maiques, S., MacKay, S. B., Rzasa, J., Sadiković, B., McConkey, H., et al. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2026.1813300
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Yaman, B., Kürekçi, F., Akbaş, S., Oney, C., Kılıç, M. A., Genç, H. M., Aslanger, A. D., & Yıldız, E. P. (2026) · Epileptic Disorders · doi:10.1002/epd2.70356
Plećaš, A., Gough, G., Kunštek, S., Babić, M., Murray, A., Nižetić, D., & Alić, I. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1963992
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Cheng, N., Lima, S., Litovchick, L., & DICKINSON, A. J. G. (2026) · Developmental Dynamics · doi:10.1002/dvdy.70192
Metadata
- 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
- Venue
- European Journal of Human Genetics
- Published
- 2015-05-06
- Volume
- 23
- Issue
- 11
- Pages
- 1473-1481
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- 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
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