ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Heterozygous variants that disturb the transcriptional repressor activity of FOXP4 cause a developmental disorder with speech/language delays and multiple congenital abnormalities.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 30 citations in OpenAlex.
- Targeted reflex RNA sequencing for enhanced variant classification on exome and genome sequencing improves patient outcomes.NPJ genomic medicine · 2026Article
- Examining Genetic Variants Associated with FOXP1 Syndrome through Molecular Dynamics of Its DNA-Binding Domain and Self-Organizing Maps.Journal of chemical information and modeling · 2026Article
- CellLoop: Identifying single-cell 3D genome chromatin loops.Nature communications · 2026Article
- Conserved sleep disturbances in FOXP1 syndrome originate from developmental dysregulation of peptidergic signaling.The Journal of clinical investigation · 2026Article
- Genomic Investigations of Spoken and Written Language Abilities: A Guide to Advances in Approaches, Technologies, and Discovery.Journal of speech, language, and hearing research : JSLHR · 2025Review
- mRNA Isoforms and Variants in Health and Disease.International journal of molecular sciences · 2025Review
- In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions.International journal of molecular sciences · 2025Article
- FOXP4 Variants Are Associated With Plateau Iris and Angle Closure Glaucoma.Investigative ophthalmology & visual science · 2025Article
- Polymorphisms of IFN signaling genes and FOXP4 influence the severity of COVID-19.BMC infectious diseases · 2024Article
- Article
- Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells, Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice.Neuroscience bulletin · 2023Article
- Characterization of the TBR1 interactome: variants associated with neurodevelopmental disorders disrupt novel protein interactions.Human molecular genetics · 2023Article
- Effects of Cortical FoxP1 Knockdowns on Learned Song Preference in Female Zebra Finches.eNeuro · 2023Article
- Approach to Cohort-Wide Re-Analysis of Exome Data in 1000 Individuals with Neurodevelopmental Disorders.Genes · 2022Article
- Downregulation of microRNA‑423‑5p suppresses TGF‑β1‑induced EMT by targeting FOXP4 in airway fibrosis.Molecular medicine reports · 2022Article
- Formation of the Mouse Internal Capsule and Cerebral Peduncle: A Pioneering Role for Striatonigral Axons as Revealed inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Underlying genetic etiologies of congenital diaphragmatic hernia.Prenatal diagnosis · 2022Review
- SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues.Cell reports · 2021Article
- Molecular networks of the FOXP2 transcription factor in the brain.EMBO reports · 2021Review
- Identification of novelFrontiers in neurologyArticle
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
purposeHeterozygous pathogenic variants in various FOXP genes cause specific developmental disorders. The phenotype associated with heterozygous variants in FOXP4 has not been previously described.
methodsWe assembled a cohort of eight individuals with heterozygous and mostly de novo variants in FOXP4: seven individuals with six different missense variants and one individual with a frameshift variant. We collected clinical data to delineate the phenotypic spectrum, and used in silico analyses and functional cell-based assays to assess pathogenicity of the variants.
resultsWe collected clinical data for six individuals: five individuals with a missense variant in the forkhead box DNA-binding domain of FOXP4, and one individual with a truncating variant. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia, cervical spine abnormalities, and ptosis. Luciferase assays showed loss-of-function effects for all these variants, and aberrant subcellular localization patterns were seen in a subset. The remaining two missense variants were located outside the functional domains of FOXP4, and showed transcriptional repressor capacities and localization patterns similar to the wild-type protein.
conclusionCollectively, our findings show that heterozygous loss-of-function variants in FOXP4 are associated with an autosomal dominant neurodevelopmental disorder with speech/language delays, growth defects, and variable congenital abnormalities.
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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.