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The aim of this study was to evaluate the contribution of genetic variants to the development of PAH in patients with APAH-CHD. Fifteen children and twenty-seven adults diagnosed with APAH-CHD were enrolled. Targeted next-generation sequencing was performed on PAH-associated genes (\n ABCC8<\/jats:italic>\n ,\n ACVRL1<\/jats:italic>\n ,\n AQP1<\/jats:italic>\n ,\n ATP13A3<\/jats:italic>\n ,\n BMPR2<\/jats:italic>\n ,\n CAV1<\/jats:italic>\n ,\n GDF2<\/jats:italic>\n ,\n GGCX<\/jats:italic>\n ,\n EIF2AK4<\/jats:italic>\n ,\n ENG<\/jats:italic>\n ,\n KCNK3<\/jats:italic>\n ,\n KDR<\/jats:italic>\n ,\n KLK1<\/jats:italic>\n ,\n SMAD1<\/jats:italic>\n ,\n SMAD4<\/jats:italic>\n ,\n SMAD9<\/jats:italic>\n ,\n SOX17<\/jats:italic>\n ,\n TBX4<\/jats:italic>\n ,\n TET2<\/jats:italic>\n ). A total of 21 distinct variants across 11 different genes were detected in 17 of the 42 patients. (\n ABCC8<\/jats:italic>\n \u2009=\u20092,\n ACVRL1<\/jats:italic>\n \u2009=\u20091,\n ATP13A3<\/jats:italic>\n \u2009=\u20092,\n BMPR2<\/jats:italic>\n \u2009=\u20094,\n GGCX<\/jats:italic>\n \u2009=\u20091,\n EIF2AK4<\/jats:italic>\n \u2009=\u20092,\n ENG<\/jats:italic>\n \u2009=\u20091,\n KDR<\/jats:italic>\n \u2009=\u20093,\n SMAD1<\/jats:italic>\n \u2009=\u20091,\n SMAD9<\/jats:italic>\n \u2009=\u20091,\n TET2<\/jats:italic>\n \u2009=\u20093). Five of the patients with the mutation were under the age of 18, and 12 patients were adults. The most common CHD in patients with detected variants was VSD. PAH-related genetic variants were not uncommon in APAH-CHD patients. Our study identified 12 novel variants that may help to understand the genetic basis of APAH-CHD.\n Trial Registration<\/jats:bold>\n The study has been registered on ClinicalTrials.gov with the identification number NCT05550389.\n <\/jats:p>","DOI":"10.1007\/s00246-025-03847-z","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T09:40:25Z","timestamp":1743846025000},"page":"821-829","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Role of Genetics in Congenital Heart Disease-Associated Pulmonary Arterial Hypertension"],"prefix":"10.1007","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0619-075X","authenticated-orcid":false,"given":"Fatma","family":"Hayvaci Canbeyli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3876-9977","authenticated-orcid":false,"given":"Kazim","family":"Secgen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9497-3118","authenticated-orcid":false,"given":"Fatih Suheyl","family":"Ezgu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0898-3905","authenticated-orcid":false,"given":"Gulten","family":"Tacoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6179-8579","authenticated-orcid":false,"given":"Serkan","family":"Unlu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3839-3201","authenticated-orcid":false,"given":"Hidayet Ozan","family":"Arabac\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3238-0752","authenticated-orcid":false,"given":"Ayhan","family":"Pektas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5446-4140","authenticated-orcid":false,"given":"Asl\u0131","family":"Inci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-3704","authenticated-orcid":false,"given":"Ergun Bar\u0131s","family":"Kaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4837-7099","authenticated-orcid":false,"given":"Umit Yasar","family":"Sinan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3145-6209","authenticated-orcid":false,"given":"Mehmet Serdar","family":"Kucukoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0728-1648","authenticated-orcid":false,"given":"Serdar","family":"Kula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"issue":"14","key":"3847_CR1","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1001\/jama.2022.4402","volume":"327","author":"NF Ruopp","year":"2022","unstructured":"Ruopp NF, Cockrill BA (2022) Diagnosis and treatment of pulmonary arterial hypertension: a review. 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