ArticleHuman genetics2021
Missense and truncating variants in CHD5 in a dominant neurodevelopmental disorder with intellectual disability, behavioral disturbances, and epilepsy.
Registry-linked trialOpen access · hybridAbstract read
In one paragraph
Article in Human genetics, 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 25 papers.
0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
What it found
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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.
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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- An episignature informed systematic analysis to ascertain the clinical significance and consequences of CHD8 missense variants.European journal of human genetics : EJHG · 2026Article
- SIMLINK enables accurate variant pathogenicity prediction through modeling the gene-variant-feature association structure.Bioinformatics (Oxford, England) · 2026Article
- Structural landscape of H3K27me3 recognition by protein domains and their potential for inhibition.The Journal of biological chemistry · 2026Review
- Genomic spectrum of congenital heart disease combined with kidney and urinary tract anomalies uncovered by exome sequencing and array-CGH.Frontiers in cell and developmental biology · 2026Article
- New Insights into the Relation between Cognition, Behavior, and theMolecular syndromology · 2025Article
- Insights into the genetic basis of bilateral head asymmetry in a scale-eating cichlid fish.Science advances · 2025Article
- Two distinct phenotypes in Snijders Blok-Campeau syndrome and characterization of the behavioral phenotype in a zebrafish model.European journal of human genetics : EJHG · 2025Article
- Molecular and clinical aspects of histone-related disorders.Human genomics · 2025Review
- It Takes a Village of Chromatin Remodelers to Regulate rDNA Expression.International journal of molecular sciences · 2025Review
- Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome.American journal of human genetics · 2025Article
- EEG Abnormalities and Phenotypic Correlates in Preschoolers with Autism Spectrum Disorder: A Single-Center Study.Journal of clinical medicine · 2025Article
- Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning.Translational psychiatry · 2024Article
- Children with Autism Spectrum Disorder and Abnormalities of Clinical EEG: A Qualitative Review.Journal of clinical medicine · 2024Review
- Divergent phenotypes in constitutive versus conditional mutant mouse models of Sifrim-Hitz-Weiss syndrome.Human molecular genetics · 2023Article
- Article
- Success and Pitfalls of Genetic Testing in Undiagnosed Diseases: Whole Exome Sequencing and Beyond.Genes · 2023Article
- Review
- Chd5 Regulates the Transcription Factor Six3 to Promote Neuronal Differentiation.Stem cells (Dayton, Ohio) · 2023Article
- Prediction of Neurodevelopmental Disorders Based on De Novo Coding Variation.Journal of autism and developmental disorders · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
45 authors at 20 institutions in 7 countries.
Ilaria Parenti *Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.ORCID http://orcid.org/0000-0002-1825-6237
Daphné Lehalle *Département de Génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Groupe Hospitalier Pitié-Salpêtrière and Hôpital Trousseau, APHP, Sorbonne Université, Paris, France.ORCID http://orcid.org/0000-0002-2193-8685
Caroline NavaInstitut du Cerveau (ICM), UMR S 1127, Inserm U1127, CNRS UMR 7225, Sorbonne Université, 75013, Paris, France.ORCID http://orcid.org/0000-0003-1272-0518
Erin TortiGeneDx, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0001-5790-1051
Elsa LeitãoInstitute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.ORCID http://orcid.org/0000-0001-5051-9714
Richard PersonGeneDx, Gaithersburg, MD, USA.
Takeshi MizuguchiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.ORCID http://orcid.org/0000-0003-4998-1244
Naomichi MatsumotoDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.ORCID http://orcid.org/0000-0001-9846-6500
Mitsuhiro KatoDepartment of Pediatrics, Showa University School of Medicine, Tokyo, 142-8666, Japan.ORCID http://orcid.org/0000-0003-1485-8553
Kazuyuki NakamuraDepartment of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, 990-9585, Japan.ORCID http://orcid.org/0000-0003-0266-9341
Stella A de ManDepartment of Pediatrics, Amphia Hospital, Breda, The Netherlands.ORCID http://orcid.org/0000-0002-3895-4649
Heidi CopeDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.ORCID http://orcid.org/0000-0003-0586-9277
Vandana ShashiDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Undiagnosed Diseases Network
Jennifer FriedmanDepartments of Neuroscience and Pediatrics, Division of Neurology, Rady Children's Hospital, UCSD, San Diego and Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
Pascal JosetInstitute of Medical Genetics, University of Zurich, Schlieren, 8952, Zurich, Switzerland.
Katharina SteindlInstitute of Medical Genetics, University of Zurich, Schlieren, 8952, Zurich, Switzerland.
Anita RauchInstitute of Medical Genetics, University of Zurich, Schlieren, 8952, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-2930-3163
Irena MuffelsDepartment of Metabolic Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands.
Peter M van HasseltDepartment of Metabolic Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0001-9821-8398
Florence PetitClinique de Génétique, CHU Lille, 59000, Lille, France.ORCID http://orcid.org/0000-0002-1368-1023
Thomas SmolInstitut de Génétique Médicale, CHRU Lille, Université de Lille, Lille, France.ORCID http://orcid.org/0000-0002-0119-5896
Gwenaël Le GuyaderService de Génétique Médicale, CHU de Poitiers, Poitiers, France.
Frédéric BilanService de Génétique Médicale, CHU de Poitiers, Poitiers, France.ORCID http://orcid.org/0000-0001-8589-6018
Arthur SorlinUnité Fonctionnelle d'Innovation Diagnostique des Maladies Rares, FHU-TRANSLAD, France Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon Bourgogne, CHU Dijon Bourgogne, Dijon, France.ORCID http://orcid.org/0000-0001-8008-9145
Antonio VitobelloUnité Fonctionnelle d'Innovation Diagnostique des Maladies Rares, FHU-TRANSLAD, France Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon Bourgogne, CHU Dijon Bourgogne, Dijon, France.ORCID http://orcid.org/0000-0003-3717-8374
Christophe PhilippeUnité Fonctionnelle d'Innovation Diagnostique des Maladies Rares, FHU-TRANSLAD, France Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon Bourgogne, CHU Dijon Bourgogne, Dijon, France.ORCID http://orcid.org/0000-0001-7098-6520
Ingrid M B H van de LaarDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-2523-1230
Marjon A van SlegtenhorstDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Philippe M CampeauCHU Sainte-Justine Research Center, Montreal, QC, H3T 1C5, Canada.ORCID http://orcid.org/0000-0001-9713-7107
Ping Yee Billie AuDepartment of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.ORCID http://orcid.org/0000-0002-9533-7217
Mitsuko NakashimaDepartment of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.ORCID http://orcid.org/0000-0001-7941-1774
Hirotomo SaitsuDepartment of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.ORCID http://orcid.org/0000-0003-0723-0960
Tatsuya YamamotoDepartment of Pediatrics, Hirosaki University Graduate School of Medicine and School of Medicine, Hirosaki, 036-8562, Japan.ORCID http://orcid.org/0000-0002-1277-5298
Yumiko NomuraDepartment of Pediatrics, Hirosaki National Hospital, Hirosaki, 036-8545, Japan.
Raymond J LouieGreenwood Genetic Center, Greenwood, SC, 29646, USA.ORCID http://orcid.org/0000-0002-6788-1151
Michael J LyonsGreenwood Genetic Center, Greenwood, SC, 29646, USA.ORCID http://orcid.org/0000-0002-8644-5507
Amy DobsonGreenwood Genetic Center, Greenwood, SC, 29646, USA.
Astrid S PlompDepartment of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
M Mahdi MotazackerLaboratory of Genome Diagnostics, Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Frank J KaiserInstitute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Andrew T TimberlakeHansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, NY, USA.ORCID http://orcid.org/0000-0002-8926-9692
Sabine A FuchsDepartment of Metabolic Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0001-9147-2406
Christel Depienne *Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany. christel.depienne@uni-due.de.ORCID http://orcid.org/0000-0002-7212-9554
Cyril Mignot *Département de Génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Groupe Hospitalier Pitié-Salpêtrière and Hôpital Trousseau, APHP, Sorbonne Université, Paris, France. cyril.mignot@aphp.fr.ORCID http://orcid.org/0000-0002-3462-3463
Centre National de la Recherche Scientifique · FRInserm · FRGreenwood Genetic Center · USUniversity Medical Center Utrecht · NLUniversity of Zurich · CHAmsterdam University Medical Centers · NLChildren’s Institute · USDuke University · USErasmus MC · NLHirosaki University · JPUniversité de Lille · FRUniversity of Calgary · CAUniversity of Duisburg-Essen · DEYokohama City University · JPAmphia Ziekenhuis · NLAomori University of Health and Welfare · JPHamamatsu University School of Medicine · JPNYU Langone Health · USShowa University · JPSorbonne Université · FR
Funding
An integrated and diverse genomic medicine program for undiagnosed diseasesU01HG007672 · NHGRI · DUKE UNIVERSITY · PI SHASHI, VANDANA · 2014 to 2022
$13.4MIntramural research grants for Neurological and Psychiatric Disorders of NCNP from the Ministry of Health, Labour and Welfare 30-6 and 30-7Japan Agency for Medical Research and Development (AMED) JP20dm0107090Japan Agency for Medical Research and Development (AMED) JP20ek0109301Japan Agency for Medical Research and Development (AMED) JP20ek0109348Japan Agency for Medical Research and Development (AMED) JP20ek0109486Japan Agency for Medical Research and Development (AMED) JP20kk0205012JSPS KAKENHI JP17H01539JSPS KAKENHI JP20K08164NHGRI NIH HHS U01 HG007672NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director U01HG007672
Abstract
Located in the critical 1p36 microdeletion region, the chromodomain helicase DNA-binding protein 5 (CHD5) gene encodes a subunit of the nucleosome remodeling and deacetylation (NuRD) complex required for neuronal development. Pathogenic variants in six of nine chromodomain (CHD) genes cause autosomal dominant neurodevelopmental disorders, while CHD5-related disorders are still unknown. Thanks to GeneMatcher and international collaborations, we assembled a cohort of 16 unrelated individuals harboring heterozygous CHD5 variants, all identified by exome sequencing. Twelve patients had de novo CHD5 variants, including ten missense and two splice site variants. Three familial cases had nonsense or missense variants segregating with speech delay, learning disabilities, and/or craniosynostosis. One patient carried a frameshift variant of unknown inheritance due to unavailability of the father. The most common clinical features included language deficits (81%), behavioral symptoms (69%), intellectual disability (64%), epilepsy (62%), and motor delay (56%). Epilepsy types were variable, with West syndrome observed in three patients, generalized tonic-clonic seizures in two, and other subtypes observed in one individual each. Our findings suggest that, in line with other CHD-related disorders, heterozygous CHD5 variants are associated with a variable neurodevelopmental syndrome that includes intellectual disability with speech delay, epilepsy, and behavioral problems as main features.
Indexed as
Mutation, MissenseAdolescentCatalytic DomainChildChild, PreschoolCohort StudiesDNA HelicasesEpilepsyFemaleGenes, DominantHumansIntellectual DisabilityMaleNerve Tissue ProteinsNeurodevelopmental DisordersPedigreeCHD5 protein, humanDNA HelicasesNerve Tissue Proteins
Identifiers
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Registered trials
NCT02450851ClinicalTrials.gov
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.