Evidence map›Paper›PMID 33743206›Full record

ArticleAmerican journal of human genetics2021

A DNA repair disorder caused by de novo monoallelic DDB1 variants is associated with a neurodevelopmental syndrome.

Susan M White, Elizabeth Bhoj, Christoffer Nellåker, Augusta M A Lachmeijer, Aren E Marshall, Kym M Boycott, Dong Li, Wendy Smith, Taila Hartley, Arran McBride and 17 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 18% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. CRL4EMBO reports · 2026
    Article
  2. Protein turnover downstream of the Nipbl/CRL4 axis contributes to abnormal development in zebrafish embryos.Developmental dynamics : an official publication of the American Association of Anatomists · 2026
    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

27 authors at 13 institutions in 7 countries.

Susan M WhiteVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address: sue.white@vcgs.org.au.
Elizabeth BhojChildren's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Christoffer NellåkerNuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK; Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford OX3 7DQ, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK.
Augusta M A LachmeijerDepartment of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, P.O. Box 85090, 3508 AB Utrecht, the Netherlands.
Aren E MarshallChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Kym M BoycottChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Dong LiChildren's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Wendy SmithDivision of Genetics, Department of Paediatrics, Maine Medical Center, Portland, ME 04012, USA.
Taila HartleyChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Arran McBrideChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Michelle E ErnstInstitute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA.
Alison S MayDivision of Child Neurology, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Dagmar WieczorekInstitut für Humangenetik, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Düsseldorf 40225, Germany.
Rami Abou JamraInstitute of Human Genetics, University Medical Center Leipzig, Leipzig 04103, Germany.
Margarete Koch-HogrebeVestische Kinder- und Jugendklinik Datteln, Universität Witten-Herdecke, Datteln 45711, Germany.
Katrin ÕunapDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, L. Puusepa 2, 51014 Tartu, Estonia; Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, L. Puusepa 2, 51014 Tartu, Estonia.
Sander PajusaluDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, L. Puusepa 2, 51014 Tartu, Estonia; Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, L. Puusepa 2, 51014 Tartu, Estonia.
K L I van GassenDepartment of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, P.O. Box 85090, 3508 AB Utrecht, the Netherlands.
Simon SadedinVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA 01242, USA.
Sara EllingwoodDivision of Genetics, Department of Paediatrics, Maine Medical Center, Portland, ME 04012, USA.
Tiong Yang TanVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC 3010, Australia.
John ChristodoulouDepartment of Paediatrics, University of Melbourne, Melbourne, VIC 3010, Australia; Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
Jaime BareaRady Children's Specialists of San Diego, San Diego, CA 92123, USA.
Paul J LockhartDepartment of Paediatrics, University of Melbourne, Melbourne, VIC 3010, Australia; Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
Care4Rare Canada ConsortiumChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Marjan M NezaratiNorth York General Hospital, Toronto, ON M2K 1E1, Canada.
Kristin D KernohanChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada; Newborn Screening Ontario, Ottawa, ON K1H 8L1, Canada.
University of Ottawa · CAThe University of Melbourne · AUChildren's Hospital of Philadelphia · USColumbia University Irving Medical Center · USMaine Medical Center · USTartu University Hospital · EEUniversity Medical Center Utrecht · NLBroad Institute · USDüsseldorf University Hospital · DELeipzig University · DENorth York General Hospital · CAUniversity of Oxford · GBWitten/Herdecke University · DE

Funding

Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
Sharing Aggregate Genomics Research Findings with Diverse Participants: A Pilot Study of an Innovative Design StrategyU01HG009599 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KOENIG, BARBARA A., KWOK, PUI-YAN · 2017 to 2021
$16.3M
CIHRMedical Research Council MR/M014568/1NHGRI NIH HHS U01 HG009599NHGRI NIH HHS UM1 HG008900
6 · The paper itself

Abstract

The DNA damage-binding protein 1 (DDB1) is part of the CUL4-DDB1 ubiquitin E3 ligase complex (CRL4), which is essential for DNA repair, chromatin remodeling, DNA replication, and signal transduction. Loss-of-function variants in genes encoding the complex components CUL4 and PHIP have been reported to cause syndromic intellectual disability with hypotonia and obesity, but no phenotype has been reported in association with DDB1 variants. Here, we report eight unrelated individuals, identified through Matchmaker Exchange, with de novo monoallelic variants in DDB1, including one recurrent variant in four individuals. The affected individuals have a consistent phenotype of hypotonia, mild to moderate intellectual disability, and similar facies, including horizontal or slightly bowed eyebrows, deep-set eyes, full cheeks, a short nose, and large, fleshy and forward-facing earlobes, demonstrated in the composite face generated from the cohort. Digital anomalies, including brachydactyly and syndactyly, were common. Three older individuals have obesity. We show that cells derived from affected individuals have altered DDB1 function resulting in abnormal DNA damage signatures and histone methylation following UV-induced DNA damage. Overall, our study adds to the growing family of neurodevelopmental phenotypes mediated by disruption of the CRL4 ubiquitin ligase pathway and begins to delineate the phenotypic and molecular effects of DDB1 misregulation.

Indexed as

AllelesMutationAdolescentChildChild, PreschoolDNA-Binding ProteinsDNA RepairFemaleHumansMaleNeurodevelopmental DisordersPhenotypeSyndromeDDB1 protein, humanDNA-Binding ProteinsCRL4DDB1intellectual disabilitymutation

Identifiers

PMID33743206
PMCPMC8059373
OpenAlexW3138961174

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.