{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:18:28Z","timestamp":1792642708291,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since 2008, <jats:italic>FOXG1<\/jats:italic> haploinsufficiency has been linked to a severe neurodevelopmental phenotype resembling Rett syndrome but with earlier onset. Most patients are unable to sit, walk, or speak. For years, <jats:italic>FOXG1<\/jats:italic> sequencing was only prescribed in such severe cases, limiting insight into the full clinical spectrum associated with this gene. Next\u2010generation sequencing (NGS) now enables unbiased diagnostics. Through the European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders, we gathered data from patients with heterozygous <jats:italic>FOXG1<\/jats:italic> variants presenting a mild phenotype, defined as able to speak and walk independently. We also reviewed data from three previously reported patients meeting our criteria. We identified five new patients with pathogenic <jats:italic>FOXG1<\/jats:italic> missense variants, primarily in the forkhead domain, showing varying nonspecific intellectual disability and developmental delay. These features are not typical of congenital Rett syndrome and were rarely associated with microcephaly and epilepsy. Our findings are consistent with a previous genotype\u2013phenotype analysis by Mitter et al. suggesting the delineation of five different <jats:italic>FOXG1<\/jats:italic> genotype groups. Milder phenotypes were associated with missense variants in the forkhead domain. This information may facilitate prognostic assessments in children carrying a <jats:italic>FOXG1<\/jats:italic> variant and improve the interpretation of new variants identified with genomic sequencing.<\/jats:p>","DOI":"10.1002\/ajmg.b.32970","type":"journal-article","created":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T04:05:42Z","timestamp":1709957142000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp><i>FOXG1<\/i><\/scp> variants can be associated with milder phenotypes than congenital Rett syndrome with unassisted walking and language development"],"prefix":"10.1002","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1788-1495","authenticated-orcid":false,"given":"Benoit","family":"Mazel","sequence":"first","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs Centre de G\u00e9n\u00e9tique, FHU TRANSLAD \u2010 CHU Dijon Bourgogne  Dijon France"},{"name":"Inserm UMR1231 GAD, G\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement Universit\u00e9 de Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Delanne","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs Centre de G\u00e9n\u00e9tique, FHU TRANSLAD \u2010 CHU Dijon Bourgogne  Dijon France"},{"name":"Centre de r\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares CHU Dijon Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3196-0453","authenticated-orcid":false,"given":"Aurore","family":"Garde","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs Centre de G\u00e9n\u00e9tique, FHU TRANSLAD \u2010 CHU Dijon Bourgogne  Dijon France"},{"name":"Inserm 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