ArticlePloS one2015
Mutation in BMPR2 Promoter: A 'Second Hit' for Manifestation of Pulmonary Arterial Hypertension?
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- A systematic review of genetic mutations in pulmonary arterial hypertension.BMC medical genetics · 2017Pooled it
- Genetic variants in pulmonary hypertension associated with chronic obstructive pulmonary disease.Current opinion in pulmonary medicine · 2026Review
- Review
- Article
- Targeting epigenetic mechanisms as an emerging therapeutic strategy in pulmonary hypertension disease.Vascular biology (Bristol, England) · 2020Article
- Epigenetic Inheritance Underlying Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Insights on the epigenetic mechanisms underlying pulmonary arterial hypertension.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018Review
- Clinical and genetic characteristics of pulmonary arterial hypertension in Lebanon.BMC medical genetics · 2018Article
- Transcriptional regulation of metabolism in disease: From transcription factors to epigenetics.PeerJ · 2018Article
- Circulating MicroRNA Markers for Pulmonary Hypertension in Supervised Exercise Intervention and Nightly Oxygen Intervention.Frontiers in physiology · 2018Article
- Genetics of Pulmonary Arterial Hypertension.Seminars in respiratory and critical care medicine · 2017Review
- Molecular and functional characterization of the BMPR2 gene in Pulmonary Arterial Hypertension.Scientific reports · 2017Article
- EIF2AK4 mutation as "second hit" in hereditary pulmonary arterial hypertension.Respiratory research · 2016Article
- Complex inheritance in Pulmonary Arterial Hypertension patients with several mutations.Scientific reports · 2016Article
- Mutational and clinical analysis of the ENG gene in patients with pulmonary arterial hypertension.BMC genetics · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHereditary pulmonary arterial hypertension (HPAH) can be caused by autosomal dominant inherited mutations of TGF-β genes, such as the bone morphogenetic protein receptor 2 (BMPR2) and Endoglin (ENG) gene. Additional modifier genes may play a role in disease manifestation and severity. In this study we prospectively assessed two families with known BMPR2 or ENG mutations clinically and genetically and screened for a second mutation in the BMPR2 promoter region.
methodsWe investigated the BMPR2 promoter region by direct sequencing in two index-patients with invasively confirmed diagnosis of HPAH, carrying a mutation in the BMPR2 and ENG gene, respectively. Sixteen family members have been assessed clinically by non-invasive methods and genetically by direct sequencing.
resultsIn both index patients with a primary BMPR2 deletion (exon 2 and 3) and Endoglin missense variant (c.1633G>A, p.(G545S)), respectively, we detected a second mutation (c.-669G>A) in the promoter region of the BMPR2 gene. The index patients with 2 mutations/variants were clinically severely affected at early age, whereas further family members with only one mutation had no manifest HPAH.
conclusionThe finding of this study supports the hypothesis that additional mutations may lead to an early and severe manifestation of HPAH. This study shows for the first time that in the regulatory region of the BMPR2 gene the promoter may be important for disease penetrance. Further studies are needed to assess the incidence and clinical relevance of mutations of the BMPR2 promoter region in a larger patient cohort.
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