{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:29:16Z","timestamp":1792798156178,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,1,7]],"date-time":"2015-01-07T00:00:00Z","timestamp":1420588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"ACTELION","id":[{"id":"https:\/\/ror.org\/001yedb91","id-type":"ROR","asserted-by":"crossref"}]},{"name":"\u201cSpanish Pulmonary Hypertension National Association\u201d (ANHP)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,12]]},"abstract":"\n Pulmonary arterial hypertension (\n PAH<\/jats:styled-content>\n ) is a pathological condition characterized by a persistent and progressive elevation of pulmonary vascular resistance with devastating consequences if untreated. In the past recent years, several genes have been related to\n PAH<\/jats:styled-content>\n , however, the molecular defect remains unknown in a significant proportion of patients with familial\n PAH<\/jats:styled-content>\n (\u223c20%). During the past few years, we have observed that\n PAH<\/jats:styled-content>\n shows a particular behavior in Iberian Gypsies, with more aggressive course and frequently affecting multiple members of the same family. We studied five Gypsy families in whom at least one individual from each family developed a severe form of\n PAH<\/jats:styled-content>\n and in whom no mutation had been identified in the common genes. We applied\n SNP<\/jats:styled-content>\n \u2010array\u2010based homozygosity mapping in three families and obtained, among others, one of which included the gene\n \n EIF2AK4<\/jats:styled-content>\n <\/jats:italic>\n , recently reported in patients with\n PAH<\/jats:styled-content>\n from group\u20101' pulmonary veno\u2010occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH). Subsequently, we sequenced\n \n EIF2AK4<\/jats:styled-content>\n <\/jats:italic>\n and found a homozygous mutation in all five families: c.\n 3344C<\/jats:styled-content>\n >T(p.\n P1115L<\/jats:styled-content>\n ). The majority of our patients required early lung transplantation. Hence, this mutation appeared with a more severe phenotype than previously reported for other\n \n EIF2AK4<\/jats:styled-content>\n <\/jats:italic>\n mutations. The finding of this novel mutation is important for genetic counseling and calculation of population recurrence risks.\n <\/jats:p>","DOI":"10.1111\/cge.12549","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T02:33:55Z","timestamp":1418697235000},"page":"579-583","source":"Crossref","is-referenced-by-count":66,"title":["A founder\n EIF2AK4<\/i>\n mutation causes an aggressive form of pulmonary arterial hypertension in Iberian Gypsies"],"prefix":"10.1111","volume":"88","author":[{"given":"J.","family":"Tenorio","sequence":"first","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras ISCIII 28029 Madrid Spain"},{"name":"INGEMM, Instituto de Gen\u00e9tica M\u00e9dica y Molecular, IdiPAZ Hospital Universitario La Paz, Madrid, Spain Universidad Aut\u00f3noma de Madrid (UAM) 28046 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Navas","sequence":"additional","affiliation":[{"name":"RIC (Red de Investigaci\u00f3n Cardiovascular) ISCIII 28029 Madrid Spain"},{"name":"Unidad Multidisciplinar de Hipertensi\u00f3n Pulmonar Servicio de Cardiolog\u00eda. Hospital Doce de Octubre Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Barrios","sequence":"additional","affiliation":[{"name":"Unidad de Cardiolog\u00eda pedi\u00e1trica Hospital Universitario Ram\u00f3n y Cajal Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras ISCIII 28029 Madrid Spain"},{"name":"INGEMM, Instituto de Gen\u00e9tica M\u00e9dica y Molecular, IdiPAZ Hospital Universitario La Paz, Madrid, Spain Universidad Aut\u00f3noma de Madrid (UAM) 28046 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Nevado","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras ISCIII 28029 Madrid Spain"},{"name":"INGEMM, Instituto de Gen\u00e9tica M\u00e9dica y Molecular, IdiPAZ Hospital Universitario La Paz, Madrid, Spain Universidad Aut\u00f3noma de Madrid (UAM) 28046 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.A.","family":"Quezada","sequence":"additional","affiliation":[{"name":"Unidad Multidisciplinar de Hipertensi\u00f3n Pulmonar Servicio de Cardiolog\u00eda. Hospital Doce de Octubre Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"L\u00f3pez\u2010Meseguer","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda Hospital Universitario Vall d' Hebron Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona Barcelonal Spain"},{"name":"CIBERES, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias ISCIII 28029 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Arias","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras ISCIII 28029 Madrid Spain"},{"name":"INGEMM, Instituto de Gen\u00e9tica M\u00e9dica y Molecular, IdiPAZ Hospital Universitario La Paz, Madrid, Spain Universidad Aut\u00f3noma de Madrid (UAM) 28046 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Mena","sequence":"additional","affiliation":[{"name":"INGEMM, Instituto de Gen\u00e9tica M\u00e9dica y Molecular, IdiPAZ Hospital Universitario La Paz, Madrid, Spain Universidad Aut\u00f3noma de Madrid (UAM) 28046 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.L.","family":"Lobo","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda Hospital Txagorritxu Vitoria Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda Hospital Central de Asturias Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Heath","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras ISCIII 28029 Madrid Spain"},{"name":"INGEMM, Instituto de Gen\u00e9tica M\u00e9dica y Molecular, IdiPAZ Hospital Universitario La Paz, Madrid, Spain Universidad Aut\u00f3noma de Madrid (UAM) 28046 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Escribano\u2010Sub\u00edas","sequence":"additional","affiliation":[{"name":"RIC (Red de Investigaci\u00f3n Cardiovascular) ISCIII 28029 Madrid Spain"},{"name":"Unidad Multidisciplinar de Hipertensi\u00f3n Pulmonar Servicio de Cardiolog\u00eda. 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