{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:28:10Z","timestamp":1792452490557,"version":"4.5.0"},"reference-count":83,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"NIH\/NHLBI","award":["R01HL137203"],"award-info":[{"award-number":["R01HL137203"]}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lethal lung developmental disorders are a rare but important group of pediatric diffuse lung diseases presenting with neonatal respiratory failure. On the basis of histopathological appearance at lung biopsy or autopsy, they have been termed: alveolar capillary dysplasia with misalignment of the pulmonary veins, acinar dysplasia, congenital alveolar dysplasia, and other unspecified primary pulmonary hypoplasias. However, the histopathological continuum in these lethal developmental disorders has made accurate diagnosis challenging, which has implications for recurrence risk. Over the past decade, genetic studies in infants with alveolar capillary dysplasia with misalignment of the pulmonary veins have revealed the causative role of the dosage-sensitiveFOXF1gene and its noncoding regulatory variants in the distant lung-specific enhancer at chromosome 16q24.1. In contrast, the molecular bases of acinar dysplasia and congenital alveolar dysplasia have remained poorly understood. Most recently, disruption of the TBX4\u2013FGF10\u2013FGFR2 epithelial\u2013mesenchymal signaling pathway has been reported in patients with these lethal pulmonary dysplasias. Application of next-generation sequencing techniques, including exome sequencing and whole-genome sequencing, has demonstrated their complex compound inheritance. These data indicate that noncoding regulatory elements play a critical role in lung development in humans. We propose that for more precise lethal lung developmental disorder diagnosis, a diagnostic pathway including whole-genome sequencing should be implemented.<\/jats:p>","DOI":"10.1164\/rccm.201903-0495tr","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T17:52:31Z","timestamp":1560361951000},"page":"1093-1101","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":75,"title":["Clinical, Histopathological, and Molecular Diagnostics in Lethal Lung Developmental Disorders"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-5618","authenticated-orcid":false,"given":"Marie","family":"Vincent","sequence":"first","affiliation":[{"name":"Service de Genetique Medicale, Centre Hospitalier Universitaire de Nantes, Nantes, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, Universit\u00e9 de Nantes, L\u2019institut du Thorax, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna A.","family":"Karolak","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics and"},{"name":"Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Deutsch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seattle Children\u2019s Hospital, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Gambin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics and"},{"name":"Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland; and"},{"name":"Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwina","family":"Popek","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"Service de Genetique Medicale, Centre Hospitalier Universitaire de Nantes, Nantes, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, Universit\u00e9 de Nantes, L\u2019institut du Thorax, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemyslaw","family":"Szafranski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Le Caignec","sequence":"additional","affiliation":[{"name":"Service 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