{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T07:36:15Z","timestamp":1771918575569,"version":"3.50.1"},"reference-count":34,"publisher":"Portland Press Ltd.","issue":"8","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4,25]]},"abstract":"<jats:p>Heritable pulmonary arterial hypertension (HPAH) is an autosomal dominantly inherited disease caused by mutations in the bone morphogenic protein receptor 2 (BMPR2) gene and\/or genes of its signalling pathway in approximately 85% of patients. We clinically and genetically analysed an HPAH family without mutations in previously described pulmonary arterial hypertension (PAH) genes. Clinical assessment included electrocardiogram, lung function, blood gas analysis, chest X-ray, laboratory testing, echocardiography and right heart catheterization in case of suspected disease. Genetic diagnostics were performed using a PAH-specific gene panel including all known 12 PAH genes and 20 further candidate genes by next-generation sequencing (NGS). HPAH was invasively confirmed in two sisters and their father who died aged 32\u00a0years. No signs of HPAH were detected in five first-degree family members. Both sisters were lung transplanted and remained stable during a follow-up of &amp;gt;20\u00a0years. We detected a novel missense mutation in the Kr\u00fcppel-like factor 2 (KLF2) likely leading to a disruption of gene function. The same KLF2 mutation has been described as a recurrent somatic mutation in B-cell lymphoma. Neither the healthy family members carried the mutation nor &amp;gt;120000 controls. These findings point to KLF2 as a new PAH gene. Further studies are needed to assess frequency and implication of KLF2 mutations in PAH patients.<\/jats:p>","DOI":"10.1042\/cs20160930","type":"journal-article","created":{"date-parts":[[2017,2,11]],"date-time":"2017-02-11T01:20:14Z","timestamp":1486776014000},"page":"689-698","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["First identification of<i>Kr\u00fcppel-like factor 2<\/i>mutation in heritable pulmonary arterial hypertension"],"prefix":"10.1042","volume":"131","author":[{"given":"Christina\u00a0A.","family":"Eichstaedt","sequence":"first","affiliation":[{"name":"Centre for Pulmonary Hypertension, Thoraxclinic at the University Hospital Heidelberg, R\u00f6ntgenstrasse 1, 69126 Heidelberg, Germany"},{"name":"Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany"},{"name":"Translational Lung Research Centre Heidelberg (TLRC), German Centre for Lung Research (DZL), Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Song","sequence":"additional","affiliation":[{"name":"Centre for Pulmonary Hypertension, Thoraxclinic at the University Hospital Heidelberg, R\u00f6ntgenstrasse 1, 69126 Heidelberg, Germany"},{"name":"Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany"},{"name":"Translational Lung Research Centre Heidelberg (TLRC), German Centre for Lung Research (DZL), Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca\u00a0Rodr\u00edguez","family":"Viales","sequence":"additional","affiliation":[{"name":"Research Unit for Genome Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zixuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Centre for Pulmonary Hypertension, Thoraxclinic at the University Hospital Heidelberg, R\u00f6ntgenstrasse 1, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Centre Heidelberg (TLRC), German Centre for Lung Research (DZL), Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Centre for Pulmonary Hypertension, Thoraxclinic at the University Hospital Heidelberg, R\u00f6ntgenstrasse 1, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Centre Heidelberg (TLRC), German Centre for Lung Research (DZL), Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius\u00a0M.","family":"Hoeper","sequence":"additional","affiliation":[{"name":"Clinic for Pneumology, Hannover Medical School, Carl-Neuberg Str 1, 30623 Hannover and German Centre for Lung Research (DZL), Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Clinic of Pulmonology, University Hospital Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Hinderhofer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekkehard","family":"Gr\u00fcnig","sequence":"additional","affiliation":[{"name":"Centre for Pulmonary Hypertension, Thoraxclinic at the University Hospital Heidelberg, R\u00f6ntgenstrasse 1, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Centre Heidelberg (TLRC), German Centre for Lung Research (DZL), Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2017,4,6]]},"reference":[{"key":"2021113011073594700_B1","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/eurheartj\/ehv317","article-title":"2015 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)","volume":"37","author":"Gali\u00e8","year":"2016","journal-title":"Eur. 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