First identification of Krüppel-like factor 2 mutation in heritable pulmonary arterial hypertension
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 wit...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
Apr 06, 2017
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| In: |
Clinical science
Year: 2017, Volume: 131, Issue: 8, Pages: 689-698 |
| ISSN: | 1470-8736 |
| DOI: | 10.1042/CS20160930 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1042/CS20160930 Verlag, Volltext: http://www.clinsci.org/content/131/8/689 
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| Author Notes: | Christina A. Eichstaedt, Jie Song, Rebecca Rodríguez Viales, Zixuan Pan, Nicola Benjamin, Christine Fischer, Marius M. Hoeper, Silvia Ulrich, Katrin Hinderhofer and Ekkehard Grünig |
| Summary: | 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 years. 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 >20 years. We detected a novel missense mutation in the Krüppel-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 >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. |
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| Item Description: | Gesehen am 28.11.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1470-8736 |
| DOI: | 10.1042/CS20160930 |