Evidence map›Paper›PMID 33438828›Full record

ArticleAmerican journal of medical genetics. Part A2021

Expansion of NEUROD2 phenotypes to include developmental delay without seizures.

Emily K Mis, Annalisa G Sega, Rebecca H Signer, Tracy Cartwright, Weizhen Ji, Julian A Martinez-Agosto, Stanley F Nelson, Christina G S Palmer, Hane Lee, Thomas Mitzelfelt and 7 more

Registry-linked trialOpen access · greenAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of medical genetics. Part A, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.7field-weighted citation impact, top 15% 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.

NCT02450851 recruitingnot on this map

Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network

TypeobservationalSponsorNational Human Genome Research Institute (NHGRI)Ran2015 to 2028Enrolled20,000ConditionsGenetic Disease
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. In Vivo Wide-Field Fluorescence CaMethods in molecular biology (Clifton, N.J.) · 2026
    Article
  2. Neurod2 knockdown inmicroPublication biology · 2026
    Article
  3. Article
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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

17 authors at 4 institutions in 2 countries.

Emily K MisPediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Annalisa G SegaPediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Rebecca H SignerDepartment of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, USA.
Tracy CartwrightCortica, San Rafael, California, USA.
Weizhen JiPediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Julian A Martinez-AgostoDeparment of Pediatrics, University of California Los Angeles, Los Angeles, California, USA.ORCID 0000-0001-6776-6949
Stanley F NelsonDepartment of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, USA.
Christina G S PalmerDepartment of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, USA.
Hane LeeDepartment of Human Genetics, University of California Los Angeles, Los Angeles, California, USA.
Thomas MitzelfeltPediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Monica KonstantinoPediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Undiagnosed Diseases Network
Lauren JeffriesPediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0002-6419-0515
Mustafa K KhokhaPediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Elysa MarcoCortica, San Rafael, California, USA.
Martin G MartinDeparment of Pediatrics, University of California Los Angeles, Los Angeles, California, USA.
Saquib A LakhaniPediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0003-3235-3460
Yale University · USUniversity of California, Los Angeles · USDominican University of California · USUniversity of California, San Francisco · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
COngenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepositoryRC2DK118640 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI James Richard Goldenring, Izumi Kaji · 2019 to 2026
$14.8M
UCLA clinical site for the investigation of undiagnosed disordersU01HG007703 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTINEZ-AGOSTO, JULIAN, NELSON, STANLEY F. · 2014 to 2022
$10.1M
A system approach to the analysis of Heterotaxy Candidate GenesR01HD102186 · NICHD · YALE UNIVERSITY · PI KHOKHA, MUSTAFA K · 2020 to 2024
$3.1M
Neurogenin3 and Intestinal FailureR01DK083762 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTIN, MARTIN G · 2009 to 2012
$1.6M
Eunice Kennedy Shriver National Institute of Child Health and Human Development 1R01HD102186NCATS NIH HHS UL1 TR001863NHGRI NIH HHS U01 HG007703NICHD NIH HHS R01 HD102186NIDDK NIH HHS R01 DK083762NIDDK NIH HHS RC2 DK118640NIH HHS U01HG007703
6 · The paper itself

Abstract

De novo heterozygous variants in the brain-specific transcription factor Neuronal Differentiation Factor 2 (NEUROD2) have been recently associated with early-onset epileptic encephalopathy and developmental delay. Here, we report an adolescent with developmental delay without seizures who was found to have a novel de novo heterozygous NEUROD2 missense variant, p.(Leu163Pro). Functional testing using an in vivo assay of neuronal differentiation in Xenopus laevis tadpoles demonstrated that the patient variant of NEUROD2 displays minimal protein activity, strongly suggesting a loss of function effect. In contrast, a second rare NEUROD2 variant, p.(Ala235Thr), identified in an adolescent with developmental delay but lacking parental studies for inheritance, showed normal in vivo NEUROD2 activity. We thus provide clinical, genetic, and functional evidence that NEUROD2 variants can lead to developmental delay without accompanying early-onset seizures, and demonstrate how functional testing can complement genetic data when determining variant pathogenicity.

Indexed as

AdolescentAnimalsBasic Helix-Loop-Helix ProteinsBrainChildDevelopmental DisabilitiesDisease Models, AnimalFemaleHeterozygoteHumansLarvaMaleNeuropeptidesPhenotypeSeizuresXenopus laevisBasic Helix-Loop-Helix ProteinsNEUROD2 protein, humanNeuropeptidesdevelopmental delayNeurod2seizure

Identifiers

PMID33438828
PMCPMC8212414
OpenAlexW3118850225

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.