{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T12:55:44Z","timestamp":1781873744524,"version":"3.54.5"},"reference-count":24,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T00:00:00Z","timestamp":1701561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["1R01HL165301-01A1"],"award-info":[{"award-number":["1R01HL165301-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Pediatr Dev Pathol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:p>Acinar dysplasia (AcDys) of the lung is a rare lethal developmental disorder in neonates characterized by severe respiratory failure and pulmonary arterial hypertension refractory to treatment. Recently, abnormalities of TBX4-FGF10-FGFR2-TMEM100 signaling regulating lung development have been reported in patients with AcDys due to heterozygous single-nucleotide variants or copy-number variant deletions involving TBX4, FGF10, or FGFR2. Here, we describe a female neonate who died at 4\u2009hours of life due to severe respiratory distress related to AcDys diagnosed by postmortem histopathologic evaluation. Genomic analyses revealed a novel deleterious heterozygous missense variant c.728A&gt;C (p.Asn243Thr) in TBX4 that arose de novo on paternal chromosome 17. We also identified 6 candidate hypomorphic rare variants in the TBX4 enhancer in trans to TBX4 coding variant. Gene expression analyses of proband\u2019s lung tissue showed a significant reduction of TMEM100 expression with near absence of TMEM100 within the endothelium of arteries and capillaries by immunohistochemistry. These results support the pathogenicity of the detected TBX4 variant and provide further evidence that disrupted signaling between TBX4 and TMEM100 may contribute to severe lung phenotypes in humans, including AcDys.<\/jats:p>","DOI":"10.1177\/10935266231213464","type":"journal-article","created":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T23:19:02Z","timestamp":1701645542000},"page":"255-259","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Diminished\n                    <i>TMEM<\/i>\n                    100 Expression in a Newborn With Acinar Dysplasia and a Novel\n                    <i>TBX4<\/i>\n                    Variant: A Case Report"],"prefix":"10.1177","volume":"27","author":[{"given":"Przemyslaw","family":"Szafranski","sequence":"first","affiliation":[{"name":"Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Patrizi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, Brigham and Women\u2019s Hospital and Newton-Wellesley Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Gambin","sequence":"additional","affiliation":[{"name":"Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushra","family":"Afzal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, Brigham and Women\u2019s Hospital and Newton-Wellesley Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Schlotterbeck","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts 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