Evidence map›Paper›PMID 25944381›Full record

ArticleEuropean journal of human genetics : EJHG2015

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

Jianling Ji, Hane Lee, Bob Argiropoulos, Naghmeh Dorrani, John Mann, Julian A Martinez-Agosto, Natalia Gomez-Ospina, Natalie Gallant, Jonathan A Bernstein, Louanne Hudgins and 23 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of human genetics : EJHG, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03624556 (Pediatric Exploratory Research Study of EGCG Use and Safety), which is not on this map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
9.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03624556 nacompletednot on this mapstarted 2018, after this paper: background citation

Pediatric Exploratory Research Study of EGCG Use and Safety (PERSEUS)

TypeinterventionalSponsorParc de Salut MarRan2018 to 2020Enrolled76ConditionsDown Syndrome, Fragile X SyndromeArmsEGCG FontUp, Placebo FontUp
3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 153 citations in OpenAlex.

  1. Sex-specific developmental phenotypes and their response to neonatalbioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Epigenetic treatment of synaptic and behavioral deficits in Dyrk1a-mutant mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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  20. Sex specific emergence of trisomicbioRxiv : the preprint server for biology · 2024
    Article

29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors at 10 institutions in 5 countries.

Jianling JiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
Hane LeeDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
Bob ArgiropoulosDepartment of Medical Genetics, Cumming School of Medicine, University of Calgary, and Alberta Children's Hospital Research Institute for Child and Maternal Health, Calgary, AB, Canada.
Naghmeh DorraniDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
John MannKaiser Permanente, Fresno, CA, USA.
Julian A Martinez-AgostoUCLA Clinical Genomics Center, Los Angeles, CA, USA.
Natalia Gomez-OspinaDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Natalie GallantDepartment of Pediatrics, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
Jonathan A BernsteinDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Louanne HudginsDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Leah SlatteryDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Bertrand IsidorCHU Nantes, Service de Génétique Médicale, and Inserm UMR957, Faculté de Médecine, Nantes, France.
Cédric Le CaignecCHU Nantes, Service de Génétique Médicale, and Inserm UMR957, Faculté de Médecine, Nantes, France.
Albert DavidCHU Nantes, Service de Génétique Médicale, and Inserm UMR957, Faculté de Médecine, Nantes, France.
Ewa ObersztynInstitute of Mother and Child, Warsaw, Poland.
Barbara Wiśniowiecka-KowalnikInstitute of Mother and Child, Warsaw, Poland.
Michelle FoxUCLA Clinical Genomics Center, Los Angeles, CA, USA.
Joshua L DeignanDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
Eric VilainDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
Emily HendricksSeattle Children's Research Institute, Seattle, WA, USA.
Margaret Horton HarrDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Sarah E NoonDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Jessi R JacksonDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Alisha WilkensDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Ghayda MirzaaSeattle Children's Research Institute, Seattle, WA, USA.
Noriko SalamonDepartment of Radiology, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
Jeff AbramsonDepartment of Physiology, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
Elaine H ZackaiDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Ian KrantzDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
A Micheil InnesDepartment of Medical Genetics, Cumming School of Medicine, University of Calgary, and Alberta Children's Hospital Research Institute for Child and Maternal Health, Calgary, AB, Canada.
Stanley F NelsonDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
Wayne W GrodyDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
Fabiola Quintero-RiveraDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
UCLA Health · USChildren's Hospital of Philadelphia · USStanford University · USUniversity of California, Los Angeles · USInserm · FRPolish Mother’s Memorial Hospital Research Institute · PLAlberta Children's Hospital · CAAlberta Children's Hospital Research InstituteInstitute for Stem Cell Biology and Regenerative Medicine · INKaiser Permanente · US

Funding

Structures of sodium glucose transporters by cryo electron microscopyR01GM078844 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ABRAMSON, JEFFREY S · 2006 to 2018
$5.3M
Genes and pathways underlying brain overgrowth and focal cortical malformationsK08NS092898 · NINDS · SEATTLE CHILDREN'S HOSPITAL · PI MIRZAA, GHAYDA · 2015 to 2019
$930k
NIGMS NIH HHS GM078844NIGMS NIH HHS R01 GM078844NINDS NIH HHS K08 NS092898
6 · The paper itself

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.

Indexed as

Abnormalities, MultipleChromosome DeletionDown SyndromeDyrk KinasesFaciesFemaleHaploinsufficiencyHumansIntellectual DisabilityMaleMicrocephalyPhenotypePolymorphism, Single NucleotideProtein Serine-Threonine KinasesProtein-Tyrosine KinasesDyrk KinasesProtein Serine-Threonine KinasesProtein-Tyrosine Kinases

Identifiers

PMID25944381
PMCPMC4613469
OpenAlexW1520236834

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.