{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T02:54:30Z","timestamp":1781578470656,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>ABCA3 is a phospholipid transporter protein required for surfactant assembly in lamellar bodies of alveolar type II cells. Biallelic pathogenic <jats:italic>ABCA3<\/jats:italic> variants cause severe neonatal respiratory distress syndrome or childhood interstitial lung disease. However, <jats:italic>ABCA3<\/jats:italic> genotype alone does not explain the diversity in disease presentation, severity, and progression. Additionally, monoallelic <jats:italic>ABCA3<\/jats:italic> variants have been reported in infants and children with ABCA3\u2010deficient phenotypes. The effects of most <jats:italic>ABCA3<\/jats:italic> variants identified in patients have not been characterized at the RNA level. <jats:italic>ABCA3<\/jats:italic> allele\u2010specific expression occurs in some cell types due to epigenetic regulation. We obtained lung tissue at transplant or autopsy from 16 infants and children with ABCA3 deficiency due to compound heterozygous <jats:italic>ABCA3<\/jats:italic> variants for biologic characterization of the predicted effects of <jats:italic>ABCA3<\/jats:italic> variants at the RNA level and determination of <jats:italic>ABCA3<\/jats:italic> allele expression. We extracted DNA and RNA from frozen lung tissue and reverse\u2010transcribed cDNA from mRNA. We performed Sanger sequencing to assess allele\u2010specific expression by comparing the heights of variant nucleotide peaks in amplicons from genomic DNA and cDNA. We found similar genomic and cDNA variant nucleotide peak heights and no evidence of allele\u2010specific expression among explant or autopsy samples with biallelic missense <jats:italic>ABCA3<\/jats:italic> variants (<jats:italic>n<\/jats:italic>\u2009=\u20096). We observed allele\u2010specific expression of missense alleles in <jats:italic>trans<\/jats:italic> with frameshift (<jats:italic>n<\/jats:italic>\u2009=\u20094) or nonsense (<jats:italic>n<\/jats:italic>\u2009=\u20091) variants, attributable to nonsense\u2010mediated decay. The missense variant c.53\u2009A\u2009&gt;\u2009G;p.Gln18Arg, located near an exon\u2010intron junction, encoded abnormal splicing with skipping of exon 4. Biologic characterization of <jats:italic>ABCA3<\/jats:italic> variants can inform discovery of variant\u2010specific disease mechanisms.<\/jats:p>","DOI":"10.1002\/ppul.25862","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T06:24:46Z","timestamp":1644992686000},"page":"1325-1330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Biologic characterization of ABCA3 variants in lung tissue from infants and children with ABCA3 deficiency"],"prefix":"10.1002","volume":"57","author":[{"given":"Kathryn K.","family":"Xu","sequence":"first","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics Washington University in St. Louis School of Medicine and St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wegner","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics Washington University in St. Louis School of Medicine and St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucille C.","family":"Geurts","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics Washington University in St. Louis School of Medicine and St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary B.","family":"Heins","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics Washington University in St. Louis School of Medicine and St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics Washington University in St. Louis School of Medicine and St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Hamvas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Ann &amp; Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirooz","family":"Eghtesady","sequence":"additional","affiliation":[{"name":"Department of Surgery Washington University in St. Louis School of Medicine and St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart C.","family":"Sweet","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics Washington University in St. Louis School of Medicine and St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Sessions Cole","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics Washington University in St. Louis School of Medicine and St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9299-0499","authenticated-orcid":false,"given":"Jennifer A.","family":"Wambach","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics Washington University in St. Louis School of Medicine and St. Louis Children's Hospital  St. Louis Missouri 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