ArticleJournal of medical genetics2003
Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia.
Article in Journal of medical genetics, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 355 citations in OpenAlex.
- Variant analysis in Chinese families with hereditary hemorrhagic telangiectasia.Molecular genetics & genomic medicine · 2019Trial
- Rapid improvement in postpartum pulmonary hypertension associated with hereditary hemorrhagic telangiectasia: A case report and review of literature.World journal of clinical cases · 2025Article
- ACVRL1 variation-induced hereditary hemorrhagic telangiectasia presenting with pulmonary arterial hypertension: clinical and genetic analyses of three case studies.BMC cardiovascular disorders · 2025Article
- High-altitude pulmonary hypertension: a comprehensive review of mechanisms and management.Clinical and experimental medicine · 2025Review
- BMP10 reflects pre-capillary pulmonary hemodynamics: association of biomarkers and hemodynamic parameters in pulmonary hypertension.Clinical research in cardiology : official journal of the German Cardiac Society · 2025Article
- Case report: Novel homozygousFrontiers in genetics · 2025Article
- Case report: Successful use of sotatercept to treat pulmonary arterial hypertension in a patient with hereditary hemorrhagic telangiectasia.Respiratory medicine case reports · 2025Article
- Case report: Use of sotatercept to treat pulmonary arterial hypertension in a patient with hereditary hemorrhagic telangiectasia.Respiratory medicine case reports · 2025Article
- Targeting Soluble TGF-β Factors: Advances in Precision Therapy for Pulmonary Arterial Hypertension.JACC. Basic to translational science · 2024Review
- Hemodynamic and Clinical Profiles of Pulmonary Arterial Hypertension Patients with GDF2 and BMPR2 Variants.International journal of molecular sciences · 2024Article
- Pathogenic Variant Frequencies in Hereditary Haemorrhagic Telangiectasia Support Clinical Evidence of Protection from Myocardial Infarction.Journal of clinical medicine · 2023Article
- Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations.Nature communications · 2023Article
- Defining the clinical validity of genes reported to cause pulmonary arterial hypertension.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Pulmonary hypertension in hereditary hemorrhagic telangiectasia: A clinical review.Pulmonary circulation · 2023Review
- Pulmonary arterial hypertension drugs can partially restore altered angiogenic capacities inPulmonary circulation · 2023Article
- Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- An emerging class of new therapeutics targeting TGF, Activin, and BMP ligands in pulmonary arterial hypertension.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Review
- Review
- New Mutations and Pathogenesis of Pulmonary Hypertension: Progress and Puzzles in Disease Pathogenesis.Circulation research · 2022Review
69 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 10 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations of the transforming growth factor beta (TGFbeta) receptor components ENDOGLIN and ALK-1 cause the autosomal dominant vascular disorder hereditary haemorrhagic telangiectasia (HHT). Heterozygous mutations of the type II receptor BMPR2 underlie familial primary pulmonary hypertension.
objectiveTo investigate kindreds presenting with both pulmonary hypertension and HHT.
methodsProbands and families were identified by specialist pulmonary hypertension centres in five countries. DNA sequence analysis of ALK-1, ENDOGLIN, and BMPR2 was undertaken. Cellular localisation was investigated by heterologous overexpression of mutant constructs in both BAEC and HeLa cells. The impact of a novel sequence variant was assessed through comparative analysis and computer modelling.
resultsMolecular analysis of 11 probands identified eight missense mutations of ALK-1, one of which was observed in two families. Mutations were located within exons 5 to 10 of the ALK-1 gene. The majority of ALK-1 mutant constructs appeared to be retained within the cell cytoplasm, in the endoplasmic reticulum. A novel GS domain mutation, when overexpressed, reached the cell surface but is predicted to disrupt conformational changes owing to loss of a critical hydrogen bond. Two novel missense mutations were identified in ENDOGLIN.
conclusionsThe association of pulmonary arterial hypertension and HHT identifies an important disease complication and appears most common among subjects with defects in ALK-1 receptor signalling. Future studies should focus on detailed molecular analysis of the common cellular pathways disrupted by mutations of ALK-1 and BMPR2 that cause inherited pulmonary vascular disease.
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