{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:23:50Z","timestamp":1791559430293,"version":"4.3.4"},"reference-count":42,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T00:00:00Z","timestamp":1545350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.ersjournals.com\/user-licence"}],"funder":[{"name":"Legs Poix"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2018,11,23]]},"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Heritable forms of pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease\/pulmonary capillary haemangiomatosis (PVOD\/PCH) diverge by lung histopathological lesions, clinical and para-clinical presentation, their responsible genes, and mode of transmission. Since the identification of the\n                      <jats:italic>BMPR2<\/jats:italic>\n                      gene in families affected by PAH, mutations in several other genes have been discovered for both forms. The mutation landscape in these new genes is not yet well known.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We set up a next-generation sequencing-based targeted sequencing gene panel allowing known genes for PAH and PVOD\/PCH to be analysed simultaneously\n                      <jats:italic>.<\/jats:italic>\n                      Genetic analysis was prospectively performed on 263 PAH and PVOD\/PCH patients (adult and paediatric cases).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pathogenic mutations were identified in 19.5% of sporadic PAH patients (n=180), 54.5% of familial PAH patients and 13.3% of PVOD\/PCH patients.\n                      <jats:italic>BMPR2<\/jats:italic>\n                      was the most frequently mutated gene, followed by\n                      <jats:italic>TBX4<\/jats:italic>\n                      in both paediatric and adult PAH.\n                      <jats:italic>BMP9<\/jats:italic>\n                      mutations were identified in 1.2% of adult PAH cases.\n                      <jats:italic>EIF2AK4<\/jats:italic>\n                      biallelic mutations were restricted to PVOD\/PCH. A truncating mutation and a predicted loss-of-function variant were also identified in\n                      <jats:italic>BMP10<\/jats:italic>\n                      in two severely affected sporadic PAH female patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our results confirm that mutations are found in genes beyond\n                      <jats:italic>BMPR2<\/jats:italic>\n                      in heritable PAH, emphasise the role of\n                      <jats:italic>TBX4<\/jats:italic>\n                      and\n                      <jats:italic>BMP9<\/jats:italic>\n                      , and designate\n                      <jats:italic>BMP10<\/jats:italic>\n                      as a new PAH gene.\n                    <\/jats:p>\n                  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