ArticleAmerican journal of human genetics2021
Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism.
Registry-linked trialAbstract readCase Reports
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. It is linked to trial NCT05528744 (Delineating the Molecular Spectrum and the Clinical, Imaging and Neuronal Phenotype of Chopra-Amiel-Gordon Syndrome), which is not on this map. Cited by 22 papers.
0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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.
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.
Delineating the Molecular Spectrum and the Clinical, Imaging and Neuronal Phenotype of Chopra-Amiel-Gordon Syndrome
Who cites it
22 citing papers in PubMed.
- Genomic dissection of hoof and leg conformation in Swiss dairy cattle populations reveals polygenic architecture and a recessive HYAL1 nonsense variant affecting longevity in Holstein cattle.Genetics, selection, evolution : GSE · 2026Article
- Integrating Polygenic Risk and Ocular Phenotyping Reveals an Axial-Length-Dominant Mechanism in High and Extreme High Myopia.Ophthalmology science · 2026Article
- Resolving Diagnostic Uncertainty in Neurodevelopmental Disorders Using Exome Sequencing Supported by Literature-Based Multi-Omics Evidence.Biomolecules · 2026Article
- A SLiM view of the human proteome.Nature structural & molecular biology · 2026Article
- A proteome-wide dependency map of protein interaction motifs.Nature structural & molecular biology · 2026Article
- Genetic architecture and clinical features of Tourette syndrome in a child and adolescent cohort: an explorative clinical exome-based study.Frontiers in psychiatry · 2026Article
- Shared Disease Mechanisms in Neurodevelopmental Disorders: A Cellular and Molecular Biology Perspective.Brain sciences · 2025Review
- Upregulating ANKHD1 in PS19 Mice Reduces Tau Phosphorylation and Mitigates Tau Toxicity-Induced Cognitive Deficits.International journal of molecular sciences · 2025Article
- Novel ANKRD17 variants implicate synaptic and mitochondrial disruptions in intellectual disability and autism spectrum disorder.Journal of neurodevelopmental disorders · 2025Article
- Whole Exome Sequencing in 26 Saudi Patients Expands the Mutational and Clinical Spectrum of Diabetic Nephropathy.Medicina (Kaunas, Lithuania) · 2025Article
- Strabismus in Genetic Syndromes: A Review.Clinical & experimental ophthalmology · 2025Review
- Nucleic acid-binding KH domain proteins influence a spectrum of biological pathways including as part of membrane-localized complexes.Journal of structural biology: X · 2024Article
- O-GlcNAc transferase congenital disorder of glycosylation (OGT-CDG): Potential mechanistic targets revealed by evaluating the OGT interactome.The Journal of biological chemistry · 2024Review
- Single-cell genomics and regulatory networks for 388 human brains.Science (New York, N.Y.) · 2024Article
- Single-cell genomics and regulatory networks for 388 human brains.bioRxiv : the preprint server for biology · 2024Article
- Case report: Whole exome sequencing reveals a novel splicing variant ofFrontiers in genetics · 2024Article
- Article
- A case of Chopra-Amiel-Gordon syndrome with a novel heterozygous variant in theSAGE open medical case reports · 2023Article
- A gene-to-patient approach uplifts novel disease gene discovery and identifies 18 putative novel disease genes.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Phenotype-driven approaches to enhance variant prioritization and diagnosis of rare disease.Human mutation · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
84 authors.
Maya ChopraDépartement de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), and Institut Imagine, Paris 75015, France; Laboratory of embryology and genetics of human malformations, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1163, Institut Imagine, Université de Paris, Paris 75015, France; Rosamund Stone Zander Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: maya.chopra@childrens.harvard.edu.
Meriel McEntagartDepartment of Medical Genetics, St George's University Hospitals NHS FT, London SW17 ORE, UK.
Jill Clayton-SmithManchester Centre for Genomic Medicine, University of Manchester, St Mary's Hospital, Manchester M13 9WL, UK; Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester M13 9WL, UK.
Konrad PlatzerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig 04129, Germany.
Anju ShuklaDepartment of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India.
Katta M GirishaDepartment of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India.
Anupriya KaurGenetics Metabolic Unit, Department of Pediatrics, PGIMER, Chandigarh 160012, India.
Parneet KaurDepartment of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India.
Rolph PfundtDepartment of Human Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, the Netherlands.
Hermine Veenstra-KnolDepartment of Genetics University of Groningen, University Medical Centre Groningen, Groningen CB50, the Netherlands.
Grazia M S ManciniDepartment of Clinical Genetics, Erasmus Medical Center, University Medical Center Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.
Gerarda CappuccioDepartment of Translational Medicine, Section of Pediatrics, Federico II University of Naples, Naples 80131, Italy; Telethon Institute of Genetics and Medicine, Pozzuoli, Naples 80078, Italy.
Nicola Brunetti-PierriDepartment of Translational Medicine, Section of Pediatrics, Federico II University of Naples, Naples 80131, Italy; Telethon Institute of Genetics and Medicine, Pozzuoli, Naples 80078, Italy.
Fanny KortümInstitute of Human Genetics and Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
Maja HempelInstitute of Human Genetics and Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
Jonas DeneckeInstitute of Human Genetics and Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
Anna LehmanDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
CAUSES StudyDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Tjitske KleefstraDepartment of Human Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, the Netherlands.
Kyra E StuurmanDepartment of Clinical Genetics, Erasmus Medical Center, University Medical Center Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.
Martina WilkeDepartment of Clinical Genetics, Erasmus Medical Center, University Medical Center Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.
Michelle L ThompsonHudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
E Martina BebinUniversity of Alabama at Birmingham, Department of Neurology and Pediatrics, Birmingham, AL 35294, USA.
Emilia K BijlsmaDepartment of Clinical Genetics, Leiden University Medical Centre, 2300 RC Leiden, the Netherlands.
Mariette J V HofferDepartment of Clinical Genetics, Leiden University Medical Centre, 2300 RC Leiden, the Netherlands.
Cacha Peeters-ScholteDepartment of Neurology, Leiden University Medical Centre, 2300 RC Leiden, the Netherlands.
Anne SlavotinekDivision of Genetics, Department of Pediatrics, UCSF, San Francisco, CA 94158, USA.
William A WeissDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94110, USA.
Tiffany YipInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
Ugur HodoglugilInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
Amy WhittleDepartment of Pediatrics, Zuckerberg San Francisco General, San Francisco, UCSF, San Francisco, CA 94143, USA.
Janette diMondaDepartment of Human Genetic, Emory University, Atlanta, GA 30322, USA.
Juanita NeiraDepartment of Human Genetic, Emory University, Atlanta, GA 30322, USA.
Sandra YangClinical Genomics Program, GeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Amelia KirbySection on Medical Genetics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Hailey PinzDivision of Medical Genetics, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Rosan LechnerDepartment of Clinical Genetics, Erasmus Medical Center, University Medical Center Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.
Frank SleutelsDepartment of Clinical Genetics, Erasmus Medical Center, University Medical Center Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.
Ingo HelbigDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19014, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Sarah McKeownDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19014, USA.
Katherine HelbigDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19014, USA.
Rebecca WillaertClinical Genomics Program, GeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Jane JuusolaClinical Genomics Program, GeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Jennifer SemotokClinical Genomics Program, GeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Medard HadonouSt. George's Genomics Service, St George's University Hospitals NHS FT, London SW17 ORE, UK.
John ShortSt. George's Genomics Service, St George's University Hospitals NHS FT, London SW17 ORE, UK.
Genomics England Research ConsortiumGenomics England, London EC1M 6BQ, UK; William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Naomi YachelevichNYU Clinical Genetics Services, 145 E 32(nd) St PH, New York, NY 10016, USA.
Sajel LalaDivision of Clinical Genetics, Nickelaus Children's Health System, 3100 SW 62(nd) Avenue, Coral Gables, FL 33155, USA.
Alberto Fernández-JaenDepartment of Pediatric Neurology. Hospital Universitario Quirónsalud, Madrid and Universidad Complutense, Madrid 28224, Spain.
Janvier Porta PelayoGenologica Center, Málaga 29016, Spain.
Chiara KlöcknerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig 04129, Germany.
Susanne B KamphausenInstitute of Human Genetics, University Hospital Magdeburg, Magdeburg 39120, Germany.
Rami Abou JamraInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig 04129, Germany.
Maria ArelinDepartment for Women and Child Health, Hospital for Children and Adolescents, University Hospitals, University of Leipzig, Leipzig 04129, Germany.
A Micheil InnesDepartment of Medical Genetics and Albert Children's Hospital Research Institute, Cumming School of Medicine, Calgary, AB T3B 6A8, Canada.
Anni NiskakoskiBlueprint Genetics, Keilaranta 16 A-B, 02150 Espoo, Finland.
Sam AminWE Genomic Medicine Centre, University Hospitals Bristol NHS Foundation Trust, Bristol B52 8EG, UK.
Maggie WilliamsBristol Genetics Laboratory, North Bristol NHS Trust, Pathology Sciences Building, Southmead Hospital, Bristol BS10 5NB, UK.
Julie EvansBristol Genetics Laboratory, North Bristol NHS Trust, Pathology Sciences Building, Southmead Hospital, Bristol BS10 5NB, UK.
Sarah SmithsonWE Genomic Medicine Centre, University Hospitals Bristol NHS Foundation Trust, Bristol B52 8EG, UK.
Damian SmedleyWilliam Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Anna de BurcaOxford Centre for Genomic Medicine, Oxford and Spires Cleft Centre, Oxford OX3 9DU, UK.
Usha KiniOxford Centre for Genomic Medicine, Oxford and Spires Cleft Centre, Oxford OX3 9DU, UK.
Martin B DelatyckiVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
Lyndon GallacherVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
Alison YeungVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
Lynn PaisBroad Institute - Center for Mendelian Genomics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Michael FieldNSW Genetics of Learning Disability Service, Waratah, NSW 2298, Australia.
Ellenore MartinNSW Genetics of Learning Disability Service, Waratah, NSW 2298, Australia.
Perrine CharlesDépartement de Génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Groupe Hospitalier Pitié Salpêtrière, AP-HP, Sorbonne Université, Paris 75013, France.
Thomas CourtinDépartement de génétique, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris 75013, France.
Boris KerenDépartement de génétique, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris 75013, France.
Maria IasconeMedical Genetics Laboratory, ASST Papa Giovanni XXIII, Bergamo 24127, Italy.
Anna CeredaPediatric Department, ASST Papa Giovanni XXIII, Bergamo 24127, Italy.
Gemma PokeGenetic Health Service, New Zealand, Central Hub Wellington Hospital, Wellington 6242, New Zealand.
Véronique AbadieDepartment of Paediatrics, Necker-Enfants Malades University Hospital, AP-HP, Centre de référence du syndrome de Pierre Robin et troubles de succion-déglutition congénitaux (SPRATON), Paris 75015, France.
Christel ChalouhiDepartment of Paediatrics, Necker-Enfants Malades University Hospital, AP-HP, Centre de référence du syndrome de Pierre Robin et troubles de succion-déglutition congénitaux (SPRATON), Paris 75015, France.
Padmini ParthasarathyDepartment of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand.
Benjamin J HallidayDepartment of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand.
Stephen P RobertsonDepartment of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand.
Stanislas LyonnetDépartement de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), and Institut Imagine, Paris 75015, France; Laboratory of embryology and genetics of human malformations, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1163, Institut Imagine, Université de Paris, Paris 75015, France.
Jeanne AmielDépartement de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), and Institut Imagine, Paris 75015, France; Laboratory of embryology and genetics of human malformations, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1163, Institut Imagine, Université de Paris, Paris 75015, France.
Christopher T GordonLaboratory of embryology and genetics of human malformations, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1163, Institut Imagine, Université de Paris, Paris 75015, France. Electronic address: chris.gordon@inserm.fr.
Funding
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MSharing 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
$16.3MA powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9MGenetic Diagnosis of Neurodevelopmental Disorders in IndiaR01HD093570 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BIELAS, STEPHANIE LEE · 2018 to 2024
$2.3MNHGRI NIH HHS R01 HG009141NHGRI NIH HHS U01 HG009599NHGRI NIH HHS UM1 HG008900NICHD NIH HHS R01 HD093570
Abstract
ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we delineate a neurodevelopmental disorder caused by de novo heterozygous ANKRD17 variants. The mutational spectrum of this cohort of 34 individuals from 32 families is highly suggestive of haploinsufficiency as the underlying mechanism of disease, with 21 truncating or essential splice site variants, 9 missense variants, 1 in-frame insertion-deletion, and 1 microdeletion (1.16 Mb). Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder.
Indexed as
HeterozygoteLoss of Function MutationAdolescentAdultChildChild, PreschoolCraniofacial AbnormalitiesFemaleHaploinsufficiencyHumansInfantIntellectual DisabilityLanguage Development DisordersMalePedigreePhenotypeANKRD17 protein, humanRNA-Binding ProteinsANKRD17ankyrin repeatsdysmorphismHippo pathwayintellectual disabilityMaskneurodevelopmental syndromespeech delayYorkie
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
NCT05528744ClinicalTrials.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.