Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID
Open accessAbstract
Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene is thought to have a major role in the neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7162 ASD/DD patients (2446 previously reported) and 2169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases with 8696 controls identified a significant enrichment of DYRK1A truncating mutations (P=0.00851) and an excess of de novo mutations (P=2.53 × 10(-10)) among ASD/intellectual disability (ID) patients. Phenotypic comparison of all novel (n=5) and recontacted (n=3) cases with previous case reports, including larger CNV and translocation events (n=7), identified a syndromal disorder among the 15 patients. It was characterized by ID, ASD, microcephaly, intrauterine growth retardation, febrile seizures in infancy, impaired speech, stereotypic behavior, hypertonia and a specific facial gestalt. We conclude that mutations in DYRK1A define a syndromic form of ASD and ID with neurodevelopmental defects consistent with murine and Drosophila knockout models.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Mutations in DYRK1A and TCF4 cause syndromic diseases presenting with microcephaly and intellectual disability.
“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 [105]
The Discussion (page unavailable) concludes that truncating DYRK1A mutations cause a syndromic form of intellectual disability characterized by microcephaly. The cited paper does not address TCF4, so it supports only the DYRK1A part of the sentence. (LLM, conf=0.89)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 36 · Cited by 204
- Authors
- van Bon, B. W. M., Coe, B. P., Bernier, R., Green, C., Gerdts, J., Witherspoon, K., Kleefstra, T., Willemsen, M. H., Kumar, R., Bosco, P., Fichera, M., Li, D., Amaral, D., Cristofoli, F., Peeters, H., Haan, E., Romano, C., Mefford, H. C., Scheffer, I., Gecz, J., de Vries, B. B. A., & Eichler, E. E.
- Affiliations
- University of Washington (US)
- Royal Children's Hospital (AU)
- Radboud University Medical Center (NL)
- The University of Adelaide (AU)
- I.R.C.C.S. Oasi Maria SS (IT)
- University of Catania (IT)
- University of California, Davis (US)
- KU Leuven (BE)
- South Australia Pathology (AU)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Eichler, E E
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2015-02-24
- Volume
- 21
- Issue
- 1
- Pages
- 126-132
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC4547916
- OpenAlex
- W1978701742
- Cited by
- 204
- References
- 36
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 17 · 2023: 13 · 2022: 14 · 2021: 24 · 2020: 20 · 2019: 12 · 2018: 44 · 2017: 20 · 2016: 17 · 2015: 4
- FWCI
- 19.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (publishedVersion)
- PubMed Central (acceptedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Lirias (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Ministerio de Economía y Competitividad
- National Institute of Mental Health (R01MH100047, R01MH101221)
- National Institute of Neurological Disorders and Stroke (R01NS069605)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083091)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- DYRK1A, de novo mutations, autism spectrum disorder, intellectual disability, syndromic autism, Down syndrome critical region, truncating mutations, microcephaly, fetal growth restriction, febrile seizures, developmental delay, phenotypic spectrum, copy number variation, neurodevelopmental disorders
- MeSH terms
- Dyrk Kinases, Adolescent, Adult, Autistic Disorder, Child, Child, Preschool, Seizures, Febrile, Female, Fetal Growth Retardation, Humans, Male, Intellectual Disability, Microcephaly, Middle Aged, Mutation, Phenotype, Protein-Tyrosine Kinases, Speech Disorders, Syndrome, Cohort Studies, Protein Serine-Threonine Kinases, Stereotypic Movement Disorder, Siblings, Young Adult
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
