First identification of Krüppel-like factor 2 mutation in heritable pulmonary arterial hypertension

• Verfasst von: Eichstaedt, Christina [VerfasserIn]
• Verfasst von: Song, Jie [VerfasserIn]
• Verfasst von: Rodríguez Viales, Rebecca [VerfasserIn]
• Verfasst von: Pan, Zixuan [VerfasserIn]
• Verfasst von: Benjamin, Nicola [VerfasserIn]
• Verfasst von: Fischer, Christine [VerfasserIn]
• Verfasst von: Hinderhofer, Katrin [VerfasserIn]
• Verfasst von: Grünig, Ekkehard [VerfasserIn]
• Titel: First identification of Krüppel-like factor 2 mutation in heritable pulmonary arterial hypertension
• Verf.angabe: Christina A. Eichstaedt, Jie Song, Rebecca Rodríguez Viales, Zixuan Pan, Nicola Benjamin, Christine Fischer, Marius M. Hoeper, Silvia Ulrich, Katrin Hinderhofer and Ekkehard Grünig
• E-Jahr: 2017
• Jahr: Apr 06, 2017
• Umfang: 10 S.
• Fussnoten: Gesehen am 28.11.2018
• Titel Quelle: Enthalten in: Clinical science
• Ort Quelle: London : Portland, 1970
• Jahr Quelle: 2017
• Band/Heft Quelle: 131(2017), 8, Seite 689-698
• ISSN Quelle: 1470-8736
• DOI: doi:10.1042/CS20160930
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1584595930

Abstract

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.