{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T16:53:30Z","timestamp":1776272010209,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL148856"],"award-info":[{"award-number":["HL148856"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Congenital alveolar dysplasia (CAD) belongs to rare lethal lung developmental disorders (LLDDs) in neonates, manifesting with acute respiratory failure and pulmonary arterial hypertension refractory to treatment. The majority of CAD cases have been associated with copy\u2010number variant (CNV) deletions at 17q23.1q23.2 or 5p12. Most CNV deletions at 17q23.1q23.2 were recurrent and encompassed two closely located genes, <jats:italic>TBX4<\/jats:italic> and <jats:italic>TBX2<\/jats:italic>. In a few CAD cases, intragenic frameshifting deletions or single\u2010nucleotide variants (SNVs) involved <jats:italic>TBX4<\/jats:italic> but not <jats:italic>TBX2<\/jats:italic>. Here, we describe a male neonate who died at 27\u2009days of life from acute respiratory failure caused by lung growth arrest along the spectrum of CAD confirmed by histopathological assessment. Trio\u2010based genome sequencing revealed in the proband a novel non\u2010recurrent ~1.07\u2009Mb heterozygous CNV deletion at 17q23.2, encompassing <jats:italic>TBX4<\/jats:italic> that arose de novo on the paternal chromosome. This is the first report of a larger\u2010sized CNV deletion in a CAD patient involving <jats:italic>TBX4<\/jats:italic> and leaving <jats:italic>TBX2<\/jats:italic> intact. Our results, together with previous reports, indicate that perturbations of <jats:italic>TBX4<\/jats:italic>, rather than <jats:italic>TBX2<\/jats:italic>, cause severe lung phenotypes in humans.<\/jats:p>","DOI":"10.1111\/cge.14428","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T01:15:25Z","timestamp":1697073325000},"page":"190-195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel non\u2010recurrent <scp>CNV<\/scp> deletion involving <scp><i>TBX4<\/i><\/scp> and leaving <scp><i>TBX2<\/i><\/scp> intact causes congenital alveolar dysplasia"],"prefix":"10.1111","volume":"105","author":[{"given":"Katarzyna","family":"Bzd\u0119ga","sequence":"first","affiliation":[{"name":"Chair and Department of Genetics and Pharmaceutical Microbiology Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3461-193X","authenticated-orcid":false,"given":"Mateusz","family":"Biela","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases Wroclaw Medical University  Wroclaw Poland"},{"name":"Department of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases Wroclaw Medical University  Wroclaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail H.","family":"Deutsch","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Kitzmiller","sequence":"additional","affiliation":[{"name":"Cincinnati Childrens Hospital Medical Center Neonatology and Pulmonary Biology  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Rydzanicz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw  Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-5526","authenticated-orcid":false,"given":"Rafa\u0142","family":"P\u0142oski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw  Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Whitsett","sequence":"additional","affiliation":[{"name":"The Perinatal Institute and Section of Neonatology Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"\u015amigiel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases Wroclaw Medical University  Wroclaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2340-4513","authenticated-orcid":false,"given":"Justyna A.","family":"Karolak","sequence":"additional","affiliation":[{"name":"Chair and Department of Genetics and Pharmaceutical Microbiology Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201903\u20100495TR"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201010\u20101697CI"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61096"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.12.010"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010020\u20100701\u20106"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.10.018"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37822"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010021\u201000902\u20100"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62656"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.038"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01965\u20102018"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102012\u2010101152"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.10.013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy146"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/144.1.249"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002866"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10208"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010021\u201001617\u2010y"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021\u20100470LE"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1207210109"}],"container-title":["Clinical 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