ArticleAmerican journal of human genetics2019
Somatic Mutations in Vascular Malformations of Hereditary Hemorrhagic Telangiectasia Result in Bi-allelic Loss of ENG or ACVRL1.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Molecular-genetic mechanisms of cerebral arteriovenous malformations: A systematic review of germline, somatic and experimental evidence.Neurosurgical review · 2026Pooled it
- Article
- Gene-Specific Endothelial Programs Drive AVM Pathogenesis inArteriosclerosis, thrombosis, and vascular biology · 2026Article
- Whole-genome resequencing with multidimensional annotation revealed pathogenic networks in sirenomelia.Italian journal of pediatrics · 2026Article
- A microphysiological system HHT-on-a-chip platform recapitulates patient vascular lesions.Nature communications · 2026Article
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Advances in the Genetics and Molecular Biology of Brain Arteriovenous Malformations.Translational stroke research · 2026Review
- Modeling Somatic Second-Hit Mutations in Novel Mouse Models of Hereditary Hemorrhagic Telangiectasia.bioRxiv : the preprint server for biology · 2026Article
- Multiple lesion-specific somatic mutations and bi-allelic loss of ACVRL1 in a single patient with hereditary haemorrhagic telangiectasia.European journal of human genetics : EJHG · 2026Article
- Vascular malformations: from genetics to therapeutics.EMBO molecular medicine · 2026Review
- Disrupted Vessels-Connected Voices: Why Patient Partnership and Cross-Disease Collaboration Are Essential for Accelerating HHT Research.Biomedicines · 2025Article
- What's new in hereditary hemorrhagic telangiectasia?Hematology. American Society of Hematology. Education Program · 2025Review
- Arteriovenous Malformations (AVMs): Molecular Pathogenesis, Clinical Features, and Emerging Therapeutic Strategies.Biomolecules · 2025Review
- Development of a functional assay for the characterisation ofJournal of medical genetics · 2025Article
- Executive summary of the 15th HHT international scientific conference.Angiogenesis · 2025Article
- Hereditary Hemorrhagic Telangiectasia Prevalence Estimates Calculated From GnomAD Allele Frequencies of Predicted Pathogenic Variants inCirculation. Genomic and precision medicine · 2025Article
- Low-Allele-Frequency Somatic Variants in a Cohort of Sporadic Saccular "Berry" Cerebral Aneurysms.Journal of the American Heart Association · 2025Article
- Common and distinct circulating microRNAs in four neurovascular disorders.Biochemistry and biophysics reports · 2025Article
- ALK1-BMPRII agonism by clustering bispecific antibodies treats hereditary hemorrhagic telangiectasia.bioRxiv : the preprint server for biology · 2025Article
- Somatic Uniparental Disomy of PTEN in Endothelial Cells Causes Vascular Malformations in Patients with PTEN Hamartoma Tumor Syndrome.Cancer discovery · 2025Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is a Mendelian disease characterized by vascular malformations (VMs) including visceral arteriovenous malformations and mucosal telangiectasia. HHT is caused by loss-of-function (LoF) mutations in one of three genes, ENG, ACVRL1, or SMAD4, and is inherited as an autosomal-dominant condition. Intriguingly, the constitutional mutation causing HHT is present throughout the body, yet the multiple VMs in individuals with HHT occur focally, rather than manifesting as a systemic vascular defect. This disconnect between genotype and phenotype suggests that a local event is necessary for the development of VMs. We investigated the hypothesis that local somatic mutations seed the formation HHT-related telangiectasia in a genetic two-hit mechanism. We identified low-frequency somatic mutations in 9/19 telangiectasia through the use of next-generation sequencing. We established phase for seven of nine samples, which confirms that the germline and somatic mutations in all seven samples exist in trans configuration; this is consistent with a genetic two-hit mechanism. These combined data suggest that bi-allelic loss of ENG or ACVRL1 may be a required event in the development of telangiectasia, and that rather than haploinsufficiency, VMs in HHT are caused by a Knudsonian two-hit mechanism.
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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.