{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:24:50Z","timestamp":1791336290325,"version":"4.3.1"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T00:00:00Z","timestamp":1578528000000},"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":["UO1 HL125218 and the JPB Foundation (WKC) and RO1 HL134802 (EDA)"],"award-info":[{"award-number":["UO1 HL125218 and the JPB Foundation (WKC) and RO1 HL134802 (EDA)"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Emerging data from studies of pediatric\u2010onset pulmonary arterial hypertension (PAH) indicate that the genomics of pediatric PAH is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 35% of pediatric\u2010onset idiopathic PAH (IPAH) compared with ~11% of adult\u2010onset IPAH. De novo variants are the most frequent genetic cause of PAH in children, likely contributing to ~15% of all cases. Rare deleterious variants in bone morphogenetic protein receptor 2 (<jats:italic>BMPR2<\/jats:italic>) contribute to pediatric\u2010onset familial PAH and IPAH with similar frequency as adult\u2010onset. While likely gene\u2010disrupting (LGD) variants in <jats:italic>BMPR2<\/jats:italic> contribute across the lifespan, damaging missense variants are more frequent in early\u2010onset PAH. Rare deleterious variants in T\u2010box 4\u2010containing protein (<jats:italic>TBX4<\/jats:italic>) are more common in pediatric\u2010compared with adult\u2010onset PAH, explaining ~8% of pediatric IPAH. PAH associated with congenital heart disease (APAH\u2010CHD) and other developmental disorders account for a large proportion of pediatric PAH. SRY\u2010related HMG box transcription factor (<jats:italic>SOX17<\/jats:italic>) was recently identified as an APAH\u2010CHD risk gene, contributing less frequently to IPAH, with a greater prevalence of rare deleterious variants in children compared with adults. The differences in genetic burden and genes underlying pediatric\u2010 vs adult\u2010onset PAH indicate that genetic information relevant to pediatric PAH cannot be extrapolated from adult studies. Large cohorts of pediatric\u2010onset PAH are necessary to identify the unique etiological differences of PAH in children, as well as the natural history and response to therapy.<\/jats:p>","DOI":"10.1002\/ppul.24637","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T18:09:13Z","timestamp":1578593353000},"page":"614-620","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Genes that drive the pathobiology of pediatric pulmonary arterial hypertension"],"prefix":"10.1002","volume":"56","author":[{"given":"Carrie L.","family":"Welch","sequence":"first","affiliation":[{"name":"Department of Pediatrics Columbia University Irving Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Austin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Vanderbilt University School of Medicine Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3438-5685","authenticated-orcid":false,"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Columbia University Irving Medical Center New York New York"},{"name":"Herbert Irving Comprehensive Cancer Center Columbia University Medical Center New York New York"},{"name":"Department of Medicine Columbia University Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/690007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200510-1668OC"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.03.575"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01916-2018"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-13-1180"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.026591"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.117.001887"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0685-z"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951116002493"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000329"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-309132"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12141"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9396"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3970"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv196"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1774-y"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007822"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12439"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1615970114"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3241"},{"key":"e_1_2_10_22_1","unstructured":"ZhuN SwietlickE WelchCL et al.Rare and de novo variants identified in 4.043 PAH cases from an international consortium implicate new PAH candidate genes. 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