ArticleGenetics in medicine : official journal of the American College of Medical Genetics2022
Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07614126 (Prospective Pilot Study of L-dopa Treatment in Patients With a Neurodevelopmental Disorder Related to a Pathogenic Variant of the CTNNB1 Gene), which is not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
8.4field-weighted citation impact, top 2% 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.
Prospective Pilot Study of L-dopa Treatment in Patients With a Neurodevelopmental Disorder Related to a Pathogenic Variant of the CTNNB1 Gene
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- A Systematic Review of Cognitive and Behavioural Symptoms in CTNNB1 Syndrome.Neuropsychology review · 2026Pooled it
- Novel CTNNB1 Gene Variants in Spanish CTNNB1 Syndrome Patients: Clinical and Psychological Manifestations.Journal of autism and developmental disorders · 2026Article
- Review
- Article
- The first description of CTNNB1 syndrome in the Tunisian population: clinical investigation, molecular docking and molecular dynamics simulation of β-catenin/E-cadherin complex.Molecular biology reports · 2025Article
- Genotype-phenotype characterization and functional reconstitution of pathogenic β-catenin variants from CTNNB1 syndrome patients.PLoS genetics · 2025Article
- An evolutionarily conserved role for CTNNB1/β-CATENIN in regulating the development of the corpus callosum.iScience · 2025Article
- RNAMolecular therapy. Nucleic acids · 2025Article
- Cognitive and Adaptive Functioning of CTNNB1 Syndrome Patients: A Comparison With Autism Spectrum Disorder and Cerebral Palsy.Journal of intellectual disability research : JIDR · 2025Article
- Gene therapy of rare diseases as a milestone in medicine - overview of the field and report on initial experiences in Slovenia.Orphanet journal of rare diseases · 2025Review
- CTNNB1 syndrome mouse models.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Monoallelic loss-of-function variants in GSK3B lead to autism and developmental delay.Molecular psychiatry · 2025Article
- Genetic advances in neurodevelopmental disorders.Medical review (2021) · 2025Review
- Genetic investigations in cerebral palsy.Developmental medicine and child neurology · 2025Review
- Uncertainties Regarding Cerebral Palsy Diagnosis: Opportunities to Clarify the Consensus Definition.Neurology. Clinical practice · 2024Article
- Motor phenotypes associated with genetic neurodevelopmental disorders.Annals of clinical and translational neurology · 2024Article
- MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway.American journal of human genetics · 2024Article
- Inhibition of GSK3α,β rescues cognitive phenotypes in a preclinical mouse model of CTNNB1 syndrome.EMBO molecular medicine · 2024Article
- Skeletal abnormalities, pediatric-onset severe osteoporosis, and multiple fragility fractures in a patient with a novelBone reports · 2024Article
- Clinical phenotypic spectrum of CTNNB1 neurodevelopmental disorder.Clinical genetics · 2024Article
Corrections and comments
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Authors and funding
75 authors at 20 institutions in 6 countries.
Sayaka KayumiAdelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.
Luis A Pérez-JuradoGenetics Service, Hospital del Mar Medical Research Institute (IMIM), Network Research Centre for Rare Diseases (CIBERER), Barcelona, Spain; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
María PalomaresInstituto de Genética Médica y Molecular (INGEMM), La Paz University Hospital, Network Research Centre for Rare Diseases (CIBERER), Madrid, Spain.
Sneha RanguAlbert Einstein College of Medicine, Bronx, NY; Section of Dermatology, Children's Hospital of Philadelphia, Philadelphia, PA.
Sarah E SheppardDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.
Wendy K ChungDepartments of Pediatrics and Medicine, Columbia University Irving Medical Center, New York, NY.
Michael C KruerPediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ; Departments of Child Health, Neurology, and Cellular & Molecular Medicine, and Program in Genetics, University of Arizona College of Medicine-Phoenix, Phoenix, AZ.
Mira KharbandaWessex Clinical Genetics Service, Southampton University Hospitals NHS Foundation Trust, Princess Anne Hospital, Southampton, United Kingdom.
David J AmorDepartment of Paediatrics, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia; Murdoch Children's Research Institute, Parkville, Victoria, Australia.
George McGillivrayMurdoch Children's Research Institute, Parkville, Victoria, Australia.
Julie S CohenDepartment of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD; Department of Neurology, Johns Hopkins University School of Medicine, Kennedy Krieger Institute, Baltimore, MD.
Sixto García-MiñaúrInstituto de Genética Médica y Molecular (INGEMM), La Paz University Hospital, Network Research Centre for Rare Diseases (CIBERER), Madrid, Spain.
Clare L van EykAdelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.
Kelly HarperAdelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.
Lachlan A JollyRobinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia; Adelaide Biomedical School, The University of Adelaide, Adelaide, South Australia, Australia.
Dani L WebberAdelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.
Christopher P BarnettPaediatric and Reproductive Genetics Unit, Women's and Children's Hospital, Adelaide, South Australia, Australia.
Fernando Santos-SimarroInstituto de Genética Médica y Molecular (INGEMM), La Paz University Hospital, Network Research Centre for Rare Diseases (CIBERER), Madrid, Spain.
Marta Pacio-MíguezInstituto de Genética Médica y Molecular (INGEMM), La Paz University Hospital, Network Research Centre for Rare Diseases (CIBERER), Madrid, Spain.
Angela Del PozoInstituto de Genética Médica y Molecular (INGEMM), La Paz University Hospital, Network Research Centre for Rare Diseases (CIBERER), Madrid, Spain.
Somayeh BakhtiariPediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ; Departments of Child Health, Neurology, and Cellular & Molecular Medicine, and Program in Genetics, University of Arizona College of Medicine-Phoenix, Phoenix, AZ.
Matthew DeardorffDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Robert's Individualized Medical Genetics Center, Children's Hospital of Philadelphia, Philadelphia, PA; Departments of Pathology and Laboratory Medicine and Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
Holly A DubbsDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA.
Kosuke IzumiDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Robert's Individualized Medical Genetics Center, Children's Hospital of Philadelphia, Philadelphia, PA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Katheryn GrandDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pediatrics, Medical Genetics, Cedars-Sinai Medical Center, Los Angeles, CA.
Christopher GrayDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Robert's Individualized Medical Genetics Center, Children's Hospital of Philadelphia, Philadelphia, PA.
Paul R MarkSpectrum Health Medical Genetics, Grand Rapids, MI.
Elizabeth J BhojDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Dong LiCenter for Applied Genomics, Children's Hospital of Philadelphia Research Institute, Philadelphia, PA.
Xilma R Ortiz-GonzalezPaediatric and Reproductive Genetics Unit, Women's and Children's Hospital, Adelaide, South Australia, Australia; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Beth KeenaDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA.
Elaine H ZackaiDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Ethan M GoldbergDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Guiomar Perez de NanclaresMolecular (epi)genetics lab, Bioaraba Research Health Institute, Araba University Hospital, Vitoria-Gasteiz, Spain.
Arrate PeredaMolecular (epi)genetics lab, Bioaraba Research Health Institute, Araba University Hospital, Vitoria-Gasteiz, Spain.
Isabel Llano-RivasDepartment of Genetics, Hospital de Cruces, Barakaldo, Spain.
Ignacio ArroyoServicio de Neonatología, Hospital San Pedro de Alcántara, Cáceres, Spain.
María Ángeles Fernández-CuestaNeuropediatrics, Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain.
Christel Thauvin-RobinetCentre de Référence Anomalies du Développement et Syndromes Malformatifs et Centre de Référence Déficiences Intellectuelles de Causes Rares, FHU TRANSLAD, CHU Dijon Bourgogne, Dijon, France; L'Unité Fonctionnelle Innovation en Diagnostic Génomique des Maladies Rares, Laboratoire de Génétique Chromosomique et Moléculaire, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France; INSERM - Bourgogne Franche-Comté University, UMR 1231 GAD Team, Genetics of Developmental Disorders, Dijon, France.
Laurence FaivreCentre de Référence Anomalies du Développement et Syndromes Malformatifs et Centre de Référence Déficiences Intellectuelles de Causes Rares, FHU TRANSLAD, CHU Dijon Bourgogne, Dijon, France; L'Unité Fonctionnelle Innovation en Diagnostic Génomique des Maladies Rares, Laboratoire de Génétique Chromosomique et Moléculaire, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France.
Aurore GardeCentre de Référence Anomalies du Développement et Syndromes Malformatifs et Centre de Référence Déficiences Intellectuelles de Causes Rares, FHU TRANSLAD, CHU Dijon Bourgogne, Dijon, France.
Benoit MazelCentre de Référence Anomalies du Développement et Syndromes Malformatifs et Centre de Référence Déficiences Intellectuelles de Causes Rares, FHU TRANSLAD, CHU Dijon Bourgogne, Dijon, France.
Ange-Line BruelL'Unité Fonctionnelle Innovation en Diagnostic Génomique des Maladies Rares, Laboratoire de Génétique Chromosomique et Moléculaire, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France; INSERM - Bourgogne Franche-Comté University, UMR 1231 GAD Team, Genetics of Developmental Disorders, Dijon, France.
Michael L TressBioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Eva BrilstraDepartment of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
Amena Smith FineDepartment of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD; Department of Neurology, Johns Hopkins University School of Medicine, Kennedy Krieger Institute, Baltimore, MD.
Kylie E CromptonDepartment of Paediatrics, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia; Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Alexander P A StegmannDepartment of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands.
Margje SinnemaDepartment of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands.
Servi C J StevensDepartment of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands.
Joost NicolaiDepartment of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands.
Gaetan LescaDepartment of Medical Genetics, Hospices Civils de Lyon, Lyon, France.
Laurence Lion-FrançoisDepartment of Pediatric Neurology, Hospices Civils de Lyon, Lyon, France.
Damien HayeDepartment of Medical Genetics, Hospices Civils de Lyon, Lyon, France.
Nicolas ChatronDepartment of Medical Genetics, Hospices Civils de Lyon, Lyon, France.
Amelie PitonDepartment of Medical genetics, Hopitaux Universitaires de Strasbourg, France.
Mathilde NizonService de Génétique Médicale, CHU Nantes, Nantes, France.
Benjamin CogneService de Génétique Médicale, CHU Nantes, Nantes, France.
Siddharth SrivastavaDepartment of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Jennifer BassettiDepartment of Pediatrics, Division of Medical Genetics, Weill Cornell Medicine, New York, NY.
Candace MussNemours/A.I duPont Hospital for Children, Wilmington, DE.
Karen W GrippNemours/A.I duPont Hospital for Children, Wilmington, DE.
Rebecca A ProcopioDepartment of Ophthalmology, Wills Eye Hospital, Philadelphia, PA.
Francisca MillanGeneDX, Gaithersburg, MD.
Michelle M MorrowGeneDX, Gaithersburg, MD.
Melissa AssafBanner Children's Specialists Neurology Clinic, Glendale, AZ.
Andres Moreno-De-LucaDepartment of Radiology, Autism & Developmental Medicine Institute, Genomic Medicine Institute, Geisinger, Danville, PA.
Shelagh JossWest of Scotland Clinical Genetics Service, Glasgow, United Kingdom.
Mark J HamiltonWest of Scotland Clinical Genetics Service, Glasgow, United Kingdom.
Marta BertoliNorthern Genetics Service, Newcastle upon Tyne, United Kingdom.
Nicola FouldsWessex Clinical Genetics Service, Southampton University Hospitals NHS Foundation Trust, Princess Anne Hospital, Southampton, United Kingdom.
Shane McKeeNorthern Ireland Regional Genetics Centre, Belfast, United Kingdom.
Alastair H MacLennanAdelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.
Jozef GeczAdelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Mark A CorbettAdelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia. Electronic address: mark.corbett@adelaide.edu.au.
Children's Hospital of Philadelphia · USThe University of Adelaide · AUHospital Universitario La Paz · ESHospices Civils de Lyon · FRMaastricht University · NLBarrow Neurological Institute · USCommunity Health Systems - Dupont Hospital · USGénétique Médicale & Génomique Fonctionelle · FRHospital Universitario Araba · ESInserm · FRKennedy Krieger Institute · USPrincess Anne Hospital · GBThe University of Melbourne · AUWomen's and Children's Hospital · AUAlbert Einstein College of Medicine · USAutism & Developmental Medicine Institute · USBoston Children's Hospital · USCedars-Sinai Medical Center · USCHU Dijon Bourgogne · FRColumbia University Irving Medical Center · US
Funding
Genomic Insights into the Neurobiology of Cerebral PalsyR01NS106298 · NINDS · UNIVERSITY OF ARIZONA · PI KRUER, MICHAEL C · 2019 to 2023
$3.7MCharacterizing the spectrum of genomic and phenotypic variation in cerebral palsyR01HD104938 · NICHD · GEISINGER CLINIC · PI Scott Myers · 2022 to 2026
$3.4MNICHD NIH HHS R01 HD104938NINDS NIH HHS R01 NS106298
Abstract
purposeGermline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) and are the most frequent, recurrent monogenic cause of cerebral palsy (CP). We investigated the range of clinical phenotypes owing to disruptions of CTNNB1 to determine the association between NEDSDV and CP.
methodsGenetic information from 404 individuals with collectively 392 pathogenic CTNNB1 variants were ascertained for the study. From these, detailed phenotypes for 52 previously unpublished individuals were collected and combined with 68 previously published individuals with comparable clinical information. The functional effects of selected CTNNB1 missense variants were assessed using TOPFlash assay.
resultsThe phenotypes associated with pathogenic CTNNB1 variants were similar. A diagnosis of CP was not significantly associated with any set of traits that defined a specific phenotypic subgroup, indicating that CP is not additional to NEDSDV. Two CTNNB1 missense variants were dominant negative regulators of WNT signaling, highlighting the utility of the TOPFlash assay to functionally assess variants.
conclusionNEDSDV is a clinically homogeneous disorder irrespective of initial clinical diagnoses, including CP, or entry points for genetic testing.
Indexed as
Intellectual DisabilityNeurodevelopmental Disordersbeta CateninGenomicsHumansPhenotypeWnt Signaling Pathwaybeta CateninCTNNB1 protein, humanAutismCerebral palsyFamilial exudative vitreoretinopathyMicrocephalyWnt beta catenin signaling pathway
Identifiers
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Registered trials
NCT07614126ClinicalTrials.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.