{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:57:20Z","timestamp":1778115440144,"version":"3.51.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) mutation is a cause of hereditary hemorrhagic telangiectasia (HHT) and\/or heritable pulmonary arterial hypertension (PAH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To describe the characteristics of patients with PAH carrying an ACVRL1 mutation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reviewed clinical, functional, and hemodynamic characteristics of 32 patients with PAH carrying an ACVRL1 mutation, corresponding to 9 patients from the French PAH Network and 23 from literature analysis. These cases were compared with 370 patients from the French PAH Network (93 with a bone morphogenetic protein receptor type 2 [BMPR2] mutation and 277 considered as idiopathic cases without identified mutation). Distribution of mutations in the ACVRL1 gene in patients with PAH was compared with the HHT Mutation Database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>At diagnosis, ACVRL1 mutation carriers were significantly younger (21.8 \u00b1 16.7 yr) than BMPR2 mutation carriers and noncarriers (35.7 \u00b1 14.9 and 47.6 \u00b1 16.3 yr, respectively; P &amp;lt; 0.0001). In seven of the nine patients from the French PAH Network, PAH diagnosis preceded manifestations of HHT. ACVRL1 mutation carriers had better hemodynamic status at diagnosis, but none responded to acute vasodilator challenge and they had shorter survival when compared with other patients with PAH despite similar use of specific therapies. ACVRL1 mutations in exon 10 were more frequently observed in patients with PAH, as compared with what was observed in the HHT Mutation Database (33.3 vs. 5%; P &amp;lt; 0.0001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ACVRL1 mutation carriers were characterized by a younger age at PAH diagnosis. Despite less severe initial hemodynamics and similar management, these patients had worse prognosis compared with other patients with PAH, suggesting more rapid disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200908-1284oc","type":"journal-article","created":{"date-parts":[[2010,1,7]],"date-time":"2010-01-07T23:45:18Z","timestamp":1262907918000},"page":"851-861","source":"Crossref","is-referenced-by-count":266,"title":["Clinical Outcomes of Pulmonary Arterial Hypertension in Patients Carrying an\n                    <i>ACVRL1<\/i>\n                    (\n                    <i>ALK1<\/i>\n                    ) Mutation"],"prefix":"10.1093","volume":"181","author":[{"given":"Barbara","family":"Girerd","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de m\u00e9decine, Kremlin Bic\u00eatre"},{"name":"Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital Antoine B\u00e9cl\u00e8re, Centre National de R\u00e9f\u00e9rence de l'Hypertension Pulmonaire S\u00e9v\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Clamart"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U999, Hypertension Art\u00e9rielle Pulmonaire: Physiopathologie et Innovation Th\u00e9rapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson"}]},{"given":"David","family":"Montani","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de m\u00e9decine, Kremlin Bic\u00eatre"},{"name":"Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital Antoine B\u00e9cl\u00e8re, Centre National de R\u00e9f\u00e9rence de l'Hypertension Pulmonaire S\u00e9v\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Clamart"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U999, Hypertension Art\u00e9rielle Pulmonaire: Physiopathologie et Innovation Th\u00e9rapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson"}]},{"given":"Florence","family":"Coulet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie-Paris 6, Laboratoire d'Oncog\u00e9n\u00e9tique et Angiog\u00e9n\u00e9tique Mol\u00e9culaire, Unit\u00e9 Mixte de Recherche en Sant\u00e9 956, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Groupe Hospitalier Piti\u00e9-Salp\u00e9tri\u00e8re, Paris; and"}]},{"given":"Benjamin","family":"Sztrymf","sequence":"additional","affiliation":[{"name":"Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital Antoine B\u00e9cl\u00e8re, Centre National de R\u00e9f\u00e9rence de l'Hypertension Pulmonaire S\u00e9v\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Clamart"}]},{"given":"Azzeddine","family":"Yaici","sequence":"additional","affiliation":[{"name":"Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital Antoine B\u00e9cl\u00e8re, Centre National de R\u00e9f\u00e9rence de l'Hypertension Pulmonaire S\u00e9v\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Clamart"}]},{"given":"Xavier","family":"Ja\u00efs","sequence":"additional","affiliation":[{"name":"Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital Antoine B\u00e9cl\u00e8re, Centre National de R\u00e9f\u00e9rence de l'Hypertension Pulmonaire S\u00e9v\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Clamart"}]},{"given":"David","family":"Tregouet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de m\u00e9decine, Kremlin Bic\u00eatre"}]},{"given":"Abilio","family":"Reis","sequence":"additional","affiliation":[{"name":"Unidade de Doen\u00e7as Respiratorias, Hospital de Santo Antonio, Centro Hospitalar do Porto, Porto, Portugal"}]},{"given":"Val\u00e9rie","family":"Drouin-Garraud","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Clinique, H\u00f4pital Charles Nicolle, Rouen; and"}]},{"given":"Alain","family":"Fraisse","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Cardiologie P\u00e9diatrique, H\u00f4pital d'Enfants de la Timone, Facult\u00e9 de M\u00e9decine de Marseille, Universit\u00e9 de la M\u00e9diterran\u00e9e, Marseille, France"}]},{"given":"Olivier","family":"Sitbon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de m\u00e9decine, Kremlin Bic\u00eatre"},{"name":"Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital Antoine B\u00e9cl\u00e8re, Centre National de R\u00e9f\u00e9rence de l'Hypertension Pulmonaire S\u00e9v\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Clamart"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U999, Hypertension Art\u00e9rielle Pulmonaire: Physiopathologie et Innovation Th\u00e9rapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson"}]},{"given":"Dermot S.","family":"O'Callaghan","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de m\u00e9decine, Kremlin Bic\u00eatre"},{"name":"Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital Antoine B\u00e9cl\u00e8re, Centre National de R\u00e9f\u00e9rence de l'Hypertension Pulmonaire S\u00e9v\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Clamart"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U999, Hypertension Art\u00e9rielle Pulmonaire: Physiopathologie et Innovation Th\u00e9rapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson"}]},{"given":"G\u00e9rald","family":"Simonneau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de m\u00e9decine, Kremlin Bic\u00eatre"},{"name":"Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital Antoine B\u00e9cl\u00e8re, Centre National de R\u00e9f\u00e9rence de l'Hypertension Pulmonaire S\u00e9v\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Clamart"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U999, Hypertension Art\u00e9rielle Pulmonaire: Physiopathologie et Innovation Th\u00e9rapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson"}]},{"given":"Florent","family":"Soubrier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie-Paris 6, Laboratoire d'Oncog\u00e9n\u00e9tique et Angiog\u00e9n\u00e9tique Mol\u00e9culaire, Unit\u00e9 Mixte de Recherche en Sant\u00e9 956, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Groupe Hospitalier Piti\u00e9-Salp\u00e9tri\u00e8re, Paris; and"}]},{"given":"Marc","family":"Humbert","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de m\u00e9decine, Kremlin Bic\u00eatre"},{"name":"Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital Antoine B\u00e9cl\u00e8re, Centre National 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