Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease.
نویسندگان
چکیده
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.
منابع مشابه
Hereditary haemorrhagic telangiectasia: a clinical analysis.
Data from 98 patients with hereditary haemorrhagic telangiectasia (HHT) are presented. All were symptomatic by 40 years of age and 62% by 16 years. Nose bleeding was the first symptom of disease in 90% of cases with mucocutaneous telangiectases appearing 5 to 20 years later. Complications of HHT are discussed and an age of onset curve given.
متن کاملHereditary haemorrhagic telangiectasia with extensive liver involvement is not caused by either HHT1 or HHT2.
Hereditary haemorrhagic telangiectasia (HHT) is a genetically heterogeneous dominant disorder. Two disease loci have been mapped to chromosomes 9q3 and 12q. In a large pedigree, with an unusually high number of patients with liver vascular malformations, both previously mapped loci have been excluded. The loci for two other inherited vascular malformation diseases, cerebral cavernous malformati...
متن کاملThe pulmonary vascular complications of hereditary haemorrhagic telangiectasia.
Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder, characterised by the presence of vascular malformations. The pulmonary vascular complications of HHT include pulmonary arteriovenous malformations, pulmonary hypertension associated with high-output heart failure and liver vascular malformations and, finally, pulmonary arterial hypertension secondary to HHT. In ...
متن کاملA new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5.
Patients with hereditary haemorrhagic telangiectasia (HHT, or Osler-Weber-Rendu syndrome) have variable presentation patterns and a high risk of preventable complications. Diagnostic tests for mutations in endoglin (HHT type 1) and ALK-1 (HHT type 2) are available. Some HHT patients are now known to have HHT-juvenile polyposis overlap syndrome due to Smad4 mutations. Families were ascertained f...
متن کاملHereditary Haemorrhagic Telangiectasia — Osler-Weber-Rendu Disease — with Extensive Hepatic Arteriovenous Malformation
Hereditary haemorrhagic telangiectasia is a rare disease. Hepatic involvement is infrequent. A patient with an extensive hepatic arteriovenous malformation is presented. Characteristic computed tomographic and angiographic findings are described followed by a review of the literature.
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ورودعنوان ژورنال:
- Journal of medical genetics
دوره 43 2 شماره
صفحات -
تاریخ انتشار 2006