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Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A
Open accessAbstract
The dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene, located on chromosome 21q22.13 within the Down syndrome critical region, has been implicated in syndromic intellectual disability associated with Down syndrome and autism. DYRK1A has a critical role in brain growth and development primarily by regulating cell proliferation, neurogenesis, neuronal plasticity and survival. Several patients have been reported with chromosome 21 aberrations such as partial monosomy, involving multiple genes including DYRK1A. In addition, seven other individuals have been described with chromosomal rearrangements, intragenic deletions or truncating mutations that disrupt specifically DYRK1A. Most of these patients have microcephaly and all have significant intellectual disability. In the present study, we report 10 unrelated individuals with DYRK1A-associated intellectual disability (ID) who display a recurrent pattern of clinical manifestations including primary or acquired microcephaly, ID ranging from mild to severe, speech delay or absence, seizures, autism, motor delay, deep-set eyes, poor feeding and poor weight gain. We identified unique truncating and non-synonymous mutations (three nonsense, four frameshift and two missense) in DYRK1A in nine patients and a large chromosomal deletion that encompassed DYRK1A in one patient. On the basis of increasing identification of mutations in DYRK1A, we suggest that this gene be considered potentially causative in patients presenting with ID, primary or acquired microcephaly, feeding problems and absent or delayed speech with or without seizures.
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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 [104]
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Metadata
- Authors
- Bronicki, L. M., Redin, C., Drunat, S., Piton, A., Lyons, M., Passemard, S., Baumann, C., Faivre, L., Thevenon, J., Rivière, J.-B., Isidor, B., Gan, G., Francannet, C., Willems, M., Gunel, M., Jones, J. R., Gleeson, J. G., Mandel, J.-L., Stevenson, R. E., Friez, M. J., & Aylsworth, A. S.
- Affiliations
- Greenwood Genetic Center (US)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Hôpital Robert-Debré (FR)
- Université de Bourgogne (FR)
- Centre Hospitalier Universitaire de Nantes (FR)
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Hôpital Arnaud de Villeneuve (FR)
- Howard Hughes Medical Institute (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Bronicki, Lucas M
- ORCID
- Venue
- European Journal of Human Genetics
- Published
- 2015-04-29
- Volume
- 23
- Issue
- 11
- Pages
- 1482-1487
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC4613470
- OpenAlex
- W2152762793
- Semantic Scholar
- 1b2b564920def54276f14fc014a0e4f850e79f19
- Cited by
- 105
- References
- 56
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 10 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 38 · 2017: 9 · 2016: 6 · 2015: 3
- FWCI
- 19.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Greenwood Genetic Center Foundation
- National Heart, Lung, and Blood Institute
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- DYRK1A, syndromic intellectual disability, Down syndrome critical region, microcephaly, truncating mutations, frameshift mutation, nonsense mutation, missense mutations, chromosomal deletion, autism spectrum disorder, speech delay, seizures, feeding difficulties, genotype-phenotype correlation
- MeSH terms
- Dyrk Kinases, Adolescent, Adult, Autistic Disorder, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 21, Down Syndrome, Female, Humans, Male, Intellectual Disability, Microcephaly, Mutation, Phenotype, Protein-Tyrosine Kinases, Protein Serine-Threonine Kinases
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