{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T23:16:06Z","timestamp":1773702966930,"version":"3.50.1"},"reference-count":28,"publisher":"Necmettin Erbakan University Press","issue":"01","funder":[{"name":"National Institutes of Health\/Eunice Kennedy Shriver National Institute","award":["R01 HD098458"],"award-info":[{"award-number":["R01 HD098458"]}]},{"name":"National Institutes of Health\/Eunice Kennedy Shriver National Institute","award":["P01 HD068250"],"award-info":[{"award-number":["P01 HD068250"]}]},{"name":"National Institutes of Health Ruth L. Kirschstein National Research Service","award":["T32 GM139534"],"award-info":[{"award-number":["T32 GM139534"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pediatr Genet"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          FOXP1 encodes a transcription factor involved in tissue regulation and cell-type-specific functions. Haploinsufficiency of FOXP1 is associated with a neurodevelopmental disorder: autosomal dominant mental retardation with language impairment with or without autistic features. More recently, heterozygous FOXP1 variants have also been shown to cause a variety of structural birth defects including central nervous system (CNS) anomalies, congenital heart defects, congenital anomalies of the kidney and urinary tract, cryptorchidism, and hypospadias. In this report, we present a previously unpublished case of an individual with congenital diaphragmatic hernia (CDH) who carries an approximately 3.8\u2009Mb deletion. Based on this deletion, and deletions previously reported in two other individuals with CDH, we define a CDH critical region on chromosome 3p13 that includes FOXP1 and four other protein-coding genes. We also provide detailed clinical descriptions of two previously reported individuals with CDH who carry de novo, pathogenic variants in FOXP1 that are predicted to trigger nonsense-mediated mRNA decay. A subset of individuals with putatively deleterious FOXP4 variants has also been shown to develop CDH. Since FOXP proteins function as homo- or heterodimers and the homologs of FOXP1 and FOXP4 are expressed at the same time points in the embryonic mouse diaphragm, they may function together as a dimer, or in parallel as homodimers, to regulate gene expression during diaphragm development. Not all individuals with heterozygous, loss-of-function changes in FOXP1 develop CDH. Hence, we conclude that FOXP1 acts as a susceptibility factor that contributes to the development of CDH in conjunction with other genetic, epigenetic, environmental, and\/or stochastic factors.<\/jats:p>","DOI":"10.1055\/s-0043-1767731","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T19:23:23Z","timestamp":1680031403000},"page":"029-034","source":"Crossref","is-referenced-by-count":4,"title":["FOXP1 Haploinsufficiency Contributes to the Development of Congenital Diaphragmatic Hernia"],"prefix":"10.53391","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9761-7303","authenticated-orcid":false,"given":"Katherine E.","family":"Pendleton","sequence":"additional","affiliation":[{"name":"Genetics and Genomics Program, Baylor College of Medicine, Houston, Texas, United States"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5343-5513","authenticated-orcid":false,"given":"Andres","family":"Hernandez-Garcia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States"},{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, Massachusetts, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3749-2884","authenticated-orcid":false,"given":"Ian M.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chad A.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Vogt","sequence":"additional","affiliation":[{"name":"West Midlands Regional Genetics Service, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances A.","family":"High","sequence":"additional","affiliation":[{"name":"Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States"},{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, Massachusetts, United States"},{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5502-4497","authenticated-orcid":false,"given":"Patricia K.","family":"Donahoe","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, Massachusetts, United States"},{"name":"Department of Surgery, Harvard Medical School, Boston, Massachusetts, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Columbia University, New York, New York, United States"},{"name":"Department of Medicine, Columbia University, New York, New York, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1460-5169","authenticated-orcid":false,"given":"Daryl A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States"},{"name":"Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"31409","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"ref1","volume-title":"Congenital Diaphragmatic Hernia Overview","author":"M Longoni","year":"1993"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0095-5108(18)30201-X","article-title":"Congenital diaphragmatic hernia. Epidemiology and outcome","volume":"23","author":"M R Langham Jr","year":"1996","journal-title":"Clin Perinatol"},{"issue":"12","key":"ref3","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1016\/j.jpedsurg.2013.08.014","article-title":"Standardized reporting for congenital diaphragmatic hernia\u2014an international consensus","volume":"48","author":"K P Lally","year":"2013","journal-title":"J Pediatr Surg"},{"issue":"04","key":"ref4","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1093\/hmg\/ddl475","article-title":"Genome-wide oligonucleotide-based array comparative genome hybridization analysis of non-isolated congenital diaphragmatic hernia","volume":"16","author":"D A Scott","year":"2007","journal-title":"Hum Mol Genet"},{"issue":"05","key":"ref5","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1086\/513442","article-title":"Genetic factors in congenital diaphragmatic hernia","volume":"80","author":"A M Holder","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1136\/jmedgenet-2020-107317","article-title":"Clinical exome sequencing data reveal high diagnostic yields for congenital diaphragmatic hernia plus (CDH+) and new phenotypic expansions involving CDH","volume":"59","author":"T M Scott","year":"2022","journal-title":"J Med Genet"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1371\/journal.pgen.0010010","article-title":"Fog2 is required for normal diaphragm and lung development in mice and humans","volume":"1","author":"K G Ackerman","year":"2005","journal-title":"PLoS Genet"},{"issue":"24","key":"ref8","first-page":"8820","article-title":"The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p","volume":"61","author":"A H Banham","year":"2001","journal-title":"Cancer Res"},{"issue":"05","key":"ref9","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ajhg.2010.09.017","article-title":"De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment","volume":"87","author":"F F Hamdan","year":"2010","journal-title":"Am J Hum Genet"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/gim.2016.131","article-title":"Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene","volume":"19","author":"M R Bekheirnia","year":"2017","journal-title":"Genet Med"},{"issue":"12","key":"ref11","doi-asserted-by":"crossref","first-page":"e1007822","DOI":"10.1371\/journal.pgen.1007822","article-title":"De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders","volume":"14","author":"H Qi","year":"2018","journal-title":"PLoS Genet"},{"issue":"01","key":"ref12","first-page":"76","article-title":"Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A","volume":"59","author":"Y Nobukuni","year":"1996","journal-title":"Am J Hum Genet"},{"issue":"04","key":"ref13","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1093\/nar\/gkw010","article-title":"Mechanism and regulation of the nonsense-mediated decay pathway","volume":"44","author":"N Hug","year":"2016","journal-title":"Nucleic Acids Res"},{"issue":"06","key":"ref14","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1001\/archpedi.1994.02170060080016","article-title":"Congenital diaphragmatic hernia in Minnesota. 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Russell","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"04","key":"ref18","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1055\/s-0038-1655755","article-title":"Prioritization of candidate genes for congenital diaphragmatic hernia in a critical region on chromosome 4p16 using a machine-learning algorithm","volume":"7","author":"D A Callaway","year":"2018","journal-title":"J Pediatr Genet"},{"issue":"06","key":"ref19","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00439-017-1774-y","article-title":"Genome-wide enrichment of damaging de novo variants in patients with isolated and complex congenital diaphragmatic hernia","volume":"136","author":"M Longoni","year":"2017","journal-title":"Hum Genet"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41436-020-01016-6","article-title":"Heterozygous variants that disturb the transcriptional repressor activity of FOXP4 cause a developmental disorder with speech\/language delays and multiple congenital abnormalities","volume":"23","author":"L S Blok","year":"2021","journal-title":"Genet Med"},{"issue":"02","key":"ref21","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1128\/MCB.24.2.809-822.2004","article-title":"Transcriptional and DNA binding activity of the Foxp1\/2\/4 family is modulated by heterotypic and homotypic protein interactions","volume":"24","author":"S Li","year":"2004","journal-title":"Mol Cell Biol"},{"issue":"05","key":"ref22","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.4049\/jimmunol.177.5.3133","article-title":"Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor","volume":"177","author":"J E Lopes","year":"2006","journal-title":"J Immunol"},{"issue":"03","key":"ref23","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/pedi.12612","article-title":"FOXP3 mutations causing early-onset insulin-requiring diabetes but without other features of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome","volume":"19","author":"J L Hwang","year":"2018","journal-title":"Pediatr Diabetes"},{"issue":"07","key":"ref24","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/intimm\/dxm043","article-title":"FOXP3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human XLAAD\/IPEX autoimmune disease","volume":"19","author":"B Li","year":"2007","journal-title":"Int Immunol"},{"issue":"05","key":"ref25","doi-asserted-by":"crossref","first-page":"e3000270","DOI":"10.1371\/journal.pbio.3000270","article-title":"Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function","volume":"17","author":"J Ren","year":"2019","journal-title":"PLoS Biol"},{"issue":"04","key":"ref26","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/ajmg.a.36960","article-title":"FBN1 contributing to familial congenital diaphragmatic 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