{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:53:39Z","timestamp":1776855219421,"version":"3.51.2"},"reference-count":41,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bases Gen\u00e9tico-Moleculares de la Medicina de Precisi\u00f3n en la Hipertensi\u00f3n Arterial Pulmonar","award":["PI 18\/01233"],"award-info":[{"award-number":["PI 18\/01233"]}]},{"name":"Bases Gen\u00e9tico-Moleculares de la Medicina de Precisi\u00f3n en la Hipertensi\u00f3n Arterial Pulmonar","award":["CM20\/00164"],"award-info":[{"award-number":["CM20\/00164"]}]},{"name":"Instituto de Salud Carlos III, Ministerio de Econom\u00eda y Competitividad, Gobierno de Espa\u00f1a","award":["PI 18\/01233"],"award-info":[{"award-number":["PI 18\/01233"]}]},{"name":"Instituto de Salud Carlos III, Ministerio de Econom\u00eda y Competitividad, Gobierno de Espa\u00f1a","award":["CM20\/00164"],"award-info":[{"award-number":["CM20\/00164"]}]},{"name":"Fondo Europeo de Desarrollo Regional, Programa Operativo Crecimiento Inteligente 2014\u20132020","award":["PI 18\/01233"],"award-info":[{"award-number":["PI 18\/01233"]}]},{"name":"Fondo Europeo de Desarrollo Regional, Programa Operativo Crecimiento Inteligente 2014\u20132020","award":["CM20\/00164"],"award-info":[{"award-number":["CM20\/00164"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI 18\/01233"],"award-info":[{"award-number":["PI 18\/01233"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CM20\/00164"],"award-info":[{"award-number":["CM20\/00164"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Pulmonary arterial hypertension (PAH) is a severe and rare disease with an important genetic background. The influence of genetic testing in the clinical classification of pediatric PAH is not well known and genetics could influence management and prognosis. Objectives: The aim of this work was to identify the molecular fingerprint of PH children in the REgistro de pacientes con HIpertensi\u00f3n Pulmonar PEDi\u00e1trica (REHIPED), and to investigate if genetics could have an impact in clinical reclassification and prognosis. Methods: We included pediatric patients with a genetic analysis from REHIPED. From 2011 onward, successive genetic techniques have been carried out. Before genetic diagnosis, patients were classified according to their clinical and hemodynamic data in five groups. After genetic analysis, the patients were reclassified. The impact of genetics in survival free of lung transplantation was estimated by Kaplan\u2013Meier curves. Results: Ninety-eight patients were included for the analysis. Before the genetic diagnoses, there were idiopathic PAH forms in 53.1%, PAH associated with congenital heart disease in 30.6%, pulmonary veno-occlusive disease\u2014PVOD\u2014in 6.1%, familial PAH in 5.1%, and associated forms with multisystemic disorders\u2014MSD\u2014in 5.1% of the patients. Pathogenic or likely pathogenic variants were found in 44 patients (44.9%). After a genetic analysis, 28.6% of the cohort was \u201creclassified\u201d, with the groups of heritable PAH, heritable PVOD, TBX4, and MSD increasing up to 18.4%, 8.2%, 4.1%, and 12.2%, respectively. The MSD forms had the worst survival rates, followed by PVOD. Conclusions: Genetic testing changed the clinical classification of a significant proportion of patients. This reclassification showed relevant prognostic implications.<\/jats:p>","DOI":"10.3390\/ijms231810433","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T22:53:46Z","timestamp":1663023226000},"page":"10433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3851-4037","authenticated-orcid":false,"given":"Alejandro","family":"Cruz-Utrilla","sequence":"first","affiliation":[{"name":"Pulmonary Hypertension Unit, ERN-Lung, Cardiology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7523-1474","authenticated-orcid":false,"given":"Natalia","family":"Gallego-Zazo","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM), Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability, 1000 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5308-2316","authenticated-orcid":false,"given":"Jair Antonio","family":"Tenorio-Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM), Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability, 1000 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inmaculada","family":"Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Unit, Department of Pediatrics, Hospital Universitario Virgen del Roc\u00edo, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3575-2427","authenticated-orcid":false,"given":"Alba","family":"Torrent-Vernetta","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Pediatric Allergy and Pulmonology Section, Department of Pediatrics, Vall d\u2019Hebron Hospital Universitari, Vall d\u2019Hebron Barcelona Hospital Campus, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amparo","family":"Moya-Bonora","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Department of Pediatrics, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Labrandero","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Department of Pediatrics, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2535-5073","authenticated-orcid":false,"given":"Mar\u00eda Elvira Garrido-Lestache","family":"Rodr\u00edguez-Monte","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Adult Congenital Heart Disease Department, Ram\u00f3n y Cajal University Hospital, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Rodr\u00edguez-Ogando","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Department of Pediatrics, Hospital Universitario Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2241-9051","authenticated-orcid":false,"given":"Mar\u00eda del Mar Rodr\u00edguez V\u00e1zquez Del","family":"Rey","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2170-6427","authenticated-orcid":false,"given":"Juana","family":"Esp\u00edn","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Hospital Universitario Virgen de la Arrixaca, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0447-9883","authenticated-orcid":false,"given":"Beatriz","family":"Plata-Izquierdo","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Hospital Universitario de Salamanca, Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Facultad de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"\u00c1lvarez-Fuente","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Adult Congenital Heart Disease Department, Ram\u00f3n y Cajal University Hospital, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2496-9786","authenticated-orcid":false,"given":"Antonio","family":"Moreno-Gald\u00f3","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Pediatric Allergy and Pulmonology Section, Department of Pediatrics, Vall d\u2019Hebron Hospital Universitari, Vall d\u2019Hebron Barcelona Hospital Campus, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6640-4839","authenticated-orcid":false,"given":"Pilar","family":"Escribano-Subias","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Unit, ERN-Lung, Cardiology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8616-8768","authenticated-orcid":false,"given":"Mar\u00eda Jes\u00fas Del Cerro","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Adult Congenital Heart Disease Department, Ram\u00f3n y Cajal University Hospital, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1378\/chest.11-1460","article-title":"An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL 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