ArticleAmerican journal of medical genetics. Part A2022
Identification and validation of a novel pathogenic variant in GDF2 (BMP9) responsible for hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations.
Article in American journal of medical genetics. Part A, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Molecular Studies on Hereditary Haemorrhagic Telangiectasia Families With Pulmonary Arteriovenous Malformations
Studies of White Blood Cells Derived From HHT Patients
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Translational relevance of animal models available on brain arteriovenous malformations, a systematic review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Pooled it
- Article
- An Ancient Founder GDF2 Variant Potentially Causes Semi-Dominant Non-Syndromic Pulmonary Arterial Hypertension.Clinical genetics · 2026Article
- A Novel Approach to Interrogating Whole Genome Sequencing Data to Optimise Clinical Utility.Molecular genetics & genomic medicine · 2026Article
- Article
- Advances in the Genetics and Molecular Biology of Brain Arteriovenous Malformations.Translational stroke research · 2026Review
- Executive summary of the 15th HHT international scientific conference.Angiogenesis · 2025Article
- Epistaxis Prevention, Treatment, and Future Perspectives for Hereditary Hemorrhagic Telangiectasia.Journal of clinical medicine · 2025Review
- Hereditary Hemorrhagic Telangiectasia Prevalence Estimates Calculated From GnomAD Allele Frequencies of Predicted Pathogenic Variants inCirculation. Genomic and precision medicine · 2025Article
- Epistaxis due to hereditary hemorrhagic telangiectasia: A case report and literature review.The Journal of international medical research · 2025Review
- The Role of Somatic Mutation in Hereditary Hemorrhagic Telangiectasia Pathogenesis.Journal of clinical medicine · 2025Review
- Clinical Phenotypes of a Pediatric Cohort withJournal of clinical medicine · 2025Article
- Prodomain processing controls BMP-10 bioactivity and targeting to fibrillin-1 in latent conformation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- Hereditary haemorrhagic telangiectasia.Nature reviews. Disease primers · 2025Review
- Updates on the Pathogenesis and Therapeutic Approaches for Hereditary Hemorrhagic Telangiectasia.Current vascular pharmacology · 2025Review
- Molecular landscape and classification of vascular anomalies.Hematology. American Society of Hematology. Education Program · 2024Review
- Somatic mutations in arteriovenous malformations in hereditary hemorrhagic telangiectasia support a bi-allelic two-hit mutation mechanism of pathogenesis.American journal of human genetics · 2024Article
- Pathophysiology in Brain Arteriovenous Malformations: Focus on Endothelial Dysfunctions and Endothelial-to-Mesenchymal Transition.Biomedicines · 2024Review
- Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances.The Journal of clinical investigation · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 7 institutions in 2 countries.
Funding
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular dysplasia, characterized by arteriovenous malformations (AVMs), mucocutaneous telangiectasia and nosebleeds. HHT is caused by a heterozygous null allele in ACVRL1, ENG, or SMAD4, which encode proteins mediating bone morphogenetic protein (BMP) signaling. Several missense and stop-gain variants identified in GDF2 (encoding BMP9) have been reported to cause a vascular anomaly syndrome similar to HHT, however none of these patients met diagnostic criteria for HHT. HHT families from UK NHS Genomic Medicine Centres were recruited to the Genomics England 100,000 Genomes Project. Whole genome sequencing and tiering protocols identified a novel, heterozygous GDF2 sequence variant in all three affected members of one HHT family who had previously screened negative for ACVRL1, ENG, and SMAD4. All three had nosebleeds and typical HHT telangiectasia, and the proband also had severe pulmonary AVMs from childhood. In vitro studies showed the mutant construct expressed the proprotein but lacked active mature BMP9 dimer, suggesting the mutation disrupts correct cleavage of the protein. Plasma BMP9 levels in the patients were significantly lower than controls. In conclusion, we propose that this heterozygous GDF2 variant is a rare cause of HHT associated with pulmonary AVMs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.