ArticleAmerican journal of human genetics2019
De Novo Pathogenic Variants in N-cadherin Cause a Syndromic Neurodevelopmental Disorder with Corpus Collosum, Axon, Cardiac, Ocular, and Genital Defects.
Article in American journal of human genetics, 2019. 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 30 papers.
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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
30 citing papers in PubMed, 50 citations in OpenAlex.
- Spatial transcriptomics profiling across tissue boundaries in the developing mouse brain.iScience · 2026Article
- Identification of a Novel CDH2 Gene Variant in an ACOGS Patient with Concurrent Respiratory Tract Infection: A Case Report.Pediatric health, medicine and therapeutics · 2026Article
- Genetic Basis of Non-Syndromic Childhood Glaucoma Associated with Anterior Segment Dysgenesis: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Excess Wnt in neurological disease.The Biochemical journal · 2025Review
- Strabismus in Genetic Syndromes: A Review.Clinical & experimental ophthalmology · 2025Review
- Multi-Omics Approach Reveals Genes and Pathways Affected in Miller-Dieker Syndrome.Molecular neurobiology · 2025Article
- Perturbed synaptic adhesion molecules signaling in neurodevelopmental disorders: The impact of metal neurotoxicity.Ibrain · 2025Review
- β-catenin-α-catenin and actomyosin signaling differentially regulate growth cone contours and axon undulation and branching of retinal ganglion cellsFrontiers in cellular neuroscience · 2025Article
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- Classical cadherins evolutionary constraints in primates is associated with their expression in the central nervous system.PloS one · 2024Article
- Homozygous CDH2 variant may be associated with hypopituitarism without neurological disorders.Endocrine connections · 2023Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Loss-of-function variants in MYCBP2 cause neurobehavioural phenotypes and corpus callosum defects.Brain : a journal of neurology · 2023Article
- Article
- Identification of a Novel Idiopathic Epilepsy Risk Locus and a Variant in theAnimals : an open access journal from MDPI · 2023Article
- Excess ribosomal protein production unbalances translation in a model of Fragile X Syndrome.Nature communications · 2022Article
- A Case of Ophthalmoplegia, Hypotonia, and Developmental Delay in the Setting of Corpus Callosum Hypoplasia.Cureus · 2022Article
- Flying under the radar: CDH2 (N-cadherin), an important hub molecule in neurodevelopmental and neurodegenerative diseases.Frontiers in neuroscience · 2022Review
- Identification of a novel variant in N-cadherin associated with dilated cardiomyopathy.Frontiers in medicine · 2022Article
- CDH2 mutation affecting N-cadherin function causes attention-deficit hyperactivity disorder in humans and mice.Nature communications · 2021Article
Corrections and comments
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Authors and funding
33 authors at 20 institutions in 11 countries.
Funding
Abstract
Cadherins constitute a family of transmembrane proteins that mediate calcium-dependent cell-cell adhesion. The extracellular domain of cadherins consists of extracellular cadherin (EC) domains, separated by calcium binding sites. The EC interacts with other cadherin molecules in cis and in trans to mechanically hold apposing cell surfaces together. CDH2 encodes N-cadherin, whose essential roles in neural development include neuronal migration and axon pathfinding. However, CDH2 has not yet been linked to a Mendelian neurodevelopmental disorder. Here, we report de novo heterozygous pathogenic variants (seven missense, two frameshift) in CDH2 in nine individuals with a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, variable axon pathfinding defects (corpus callosum agenesis or hypoplasia, mirror movements, Duane anomaly), and ocular, cardiac, and genital anomalies. All seven missense variants (c.1057G>A [p.Asp353Asn]; c.1789G>A [p.Asp597Asn]; c.1789G>T [p.Asp597Tyr]; c.1802A>C [p.Asn601Thr]; c.1839C>G [p.Cys613Trp]; c.1880A>G [p.Asp627Gly]; c.2027A>G [p.Tyr676Cys]) result in substitution of highly conserved residues, and six of seven cluster within EC domains 4 and 5. Four of the substitutions affect the calcium-binding site in the EC4-EC5 interdomain. We show that cells expressing these variants in the EC4-EC5 domains have a defect in cell-cell adhesion; this defect includes impaired binding in trans with N-cadherin-WT expressed on apposing cells. The two frameshift variants (c.2563_2564delCT [p.Leu855Valfs
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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.