Genetics and genomics of pulmonary arterial hypertension
Top Cited Papers
Open Access
- 31 December 2018
- journal article
- conference paper
- Published by European Respiratory Society (ERS) in European Respiratory Journal
- Vol. 53 (1), 1801899
- https://doi.org/10.1183/13993003.01899-2018
Abstract
Since 2000 there have been major advances in our understanding of the genetic and genomics of pulmonary arterial hypertension (PAH), although there remains much to discover. Based on existing knowledge, around 25-30% of patients diagnosed with idiopathic PAH have an underlying Mendelian genetic cause for their condition and should be classified as heritable PAH (HPAH). Here, we summarise the known genetic and genomic drivers of PAH, the insights these provide into pathobiology, and the opportunities afforded for development of novel therapeutic approaches. In addition, factors determining the incomplete penetrance observed in HPAH are discussed. The currently available approaches to genetic testing and counselling, and the impact of a genetic diagnosis on clinical management of the patient with PAH, are presented. Advances in DNA sequencing technology are rapidly expanding our ability to undertake genomic studies at scale in large cohorts. In the future, such studies will provide a more complete picture of the genetic contribution to PAH and, potentially, a molecular classification of this disease.Keywords
This publication has 75 references indexed in Scilit:
- Identification of rare sequence variation underlying heritable pulmonary arterial hypertensionNature Communications, 2018
- BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysisThe Lancet Respiratory Medicine, 2016
- A Novel Channelopathy in Pulmonary Arterial HypertensionThe New England Journal of Medicine, 2013
- Whole Exome Sequencing to Identify a Novel Gene (Caveolin-1) Associated With Human Pulmonary Arterial HypertensionCirculation: Cardiovascular Genetics, 2012
- Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertensionHuman Mutation, 2011
- A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertensionJournal of Medical Genetics, 2009
- Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta familyJournal of Medical Genetics, 2000
- Heterozygous germline mutations in BMPR2, encoding a TGF-β receptor, cause familial primary pulmonary hypertensionNature Genetics, 2000
- Familial Primary Pulmonary Hypertension (Gene PPH1) Is Caused by Mutations in the Bone Morphogenetic Protein Receptor–II GeneAmerican Journal of Human Genetics, 2000
- Familial primary pulmonary hypertension: clinical patterns.Published by Elsevier BV ,1984