Hereditary Haemorrhagic Telangiectasia: Current Views on Genetics and Mechanisms of Disease

Overview

Journal J Med Genet

Specialty Genetics

Date 2005 May 10

PMID 15879500

Citations 140

Authors

S A Abdalla

M Letarte

Affiliations

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Abstract

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by epistaxis, telangiectases, and multiorgan vascular dysplasia. The two major types of disease, HHT1 and HHT2, are caused by mutations in the ENG (endoglin) and ACVRL1 genes, respectively. The corresponding endoglin and ALK-1 proteins are specific endothelial receptors of the transforming growth factor beta superfamily essential for maintaining vascular integrity. Many mutations have been identified in ENG and ACVRL1 genes and support the haploinsufficiency model for HHT. Two more genes have recently been implicated in HHT: MADH4 mutated in a combined syndrome of juvenile polyposis and HHT (JPHT), and an unidentified HHT3 gene linked to chromosome 5. Current knowledge on the genetics of HHT is summarised, including the pathways that link the genes responsible for HHT and the potential mechanisms underlying the pathogenesis of the disease.

Citing Articles

Diagnostic and Prognostic Value of Angiogenic Status in Hereditary Hemorrhagic Telangiectasia.

Jaimes-Diaz S, Juan-Samper G, Torres-Martinez S, Escorihuela-Alares E, Calabuig-Farinas S, Rodriguez-Lopez R Diagnostics (Basel). 2025; 14(24.

PMID: 39767144 PMC: 11674149. DOI: 10.3390/diagnostics14242783.

Overlap syndrome of hereditary hemorrhagic telangiectasia and juvenile polyposis syndrome: ten years follow-up-case series and review of literature.

Gonzalez M, Vazquez C, Arguero M, Santino J, Braslavsky A, Serra M Fam Cancer. 2024; 24(1):1.

PMID: 39546055 DOI: 10.1007/s10689-024-00425-9.

Arterial-Lymphatic-Like Endothelial Cells Appear in Hereditary Hemorrhagic Telangiectasia 2 and Contribute to Vascular Leakage and Arteriovenous Malformations.

Yang Y, Wu X, Zhao Y, Zhang D, Zhang L, Cai X Circulation. 2024; 151(5):299-317.

PMID: 39429196 PMC: 11789604. DOI: 10.1161/CIRCULATIONAHA.124.070925.

Molecular and Functional Cargo of Plasma-Derived Exosomes in Patients with Hereditary Hemorrhagic Telangiectasia.

Wang Y, Hofmann L, Huber D, Lochbaum R, Ludwig S, Brunner C J Clin Med. 2024; 13(18).

PMID: 39336917 PMC: 11432581. DOI: 10.3390/jcm13185430.

Investigation of the Genetic Determinants of Telangiectasia and Solid Organ Arteriovenous Malformation Formation in Hereditary Hemorrhagic Telangiectasia (HHT).

Whitehead K, Toydemir D, Wooderchak-Donahue W, Oakley G, McRae B, Putnam A Int J Mol Sci. 2024; 25(14).

PMID: 39062925 PMC: 11276621. DOI: 10.3390/ijms25147682.

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