{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:08:11Z","timestamp":1790647691884,"version":"4.1.0"},"reference-count":8,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>De novo variants in <jats:italic>FOXP4<\/jats:italic> were recently associated with a neurodevelopmental disorder characterized by speech and language delay, growth abnormalities, hypotonia, and variable congenital abnormalities, including congenital diaphragmatic hernia, cervical spine abnormalities, strabismus, cryptorchidism, and ptosis. The variant spectrum in this small cohort was limited to de novo missense except for one frameshift, the inheritance of which was unknown. Variants tested in vitro exhibited reduced repressor transcriptional activity, indicating loss of function is the likely mechanism of disease, but only one frameshift variant was reported. Here, we report four affected individuals from two unrelated families heterozygous for a nonsense variant, c.1893C\u2009&gt;\u2009G, p.Tyr631*, in <jats:italic>FOXP4<\/jats:italic>. The phenotype of the affected children includes developmental delay, feeding difficulties in infancy, and similar facial features. In both cases, the variant was inherited from a parent with mild or even subclinical features. Interestingly, one patient presented with congenital diaphragmatic hernia, as reported in two other <jats:italic>FOXP4<\/jats:italic> patients. This report implicates <jats:italic>FOXP4<\/jats:italic> truncating variants in human disease and highlights the wide phenotypic spectrum and variable expressivity.<\/jats:p>","DOI":"10.1002\/ajmg.a.63006","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T13:39:32Z","timestamp":1666877972000},"page":"259-264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Recurrent <scp><i>FOXP4<\/i><\/scp> nonsense variant in two unrelated patients: Association with neurodevelopmental disease and congenital diaphragmatic hernia"],"prefix":"10.1002","volume":"191","author":[{"given":"Florencia","family":"Del Viso","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Mercy Hospital  Kansas City Missouri 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