Article Text

Download PDFPDF
No live individual homozygous for a novel endoglin mutation was found in a consanguineous Arab family with hereditary haemorrhagic telangiectasia
  1. A Karabegovic1,*,
  2. M Shinawi2,*,
  3. U Cymerman1,
  4. M Letarte1
  1. 1Cancer Research Program, The Hospital for Sick Children, Toronto, Canada
  2. 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  1. Correspondence to:
 Dr Marwan Shinawi
 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA;

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Hereditary haemorrhagic telangiectasia (HHT or Rendu-Osler-Weber syndrome; MIM 187300) is characterised by vascular dysplasia and is inherited in an autosomal dominant manner. HHT occurs among many ethnic groups over a wide geographical area. Recent epidemiological studies have revealed an incidence for this disease of 1 in 5000–8000.1,2 In most cases, the manifestations of HHT are not present at birth, but develop with age; epistaxis is usually the earliest sign, often occurring in childhood, while mucocutaneous and gastrointestinal telangiectases develop progressively with age.3 Arteriovenous malformations (AVMs) in the pulmonary, cerebral, or hepatic circulations account for some of the most devastating clinical complications of HHT and are due to direct connections between arteries and veins.4 The shunting of blood through these lesions can lead to serious complications such as hypoxemia, stroke, brain abscess, heart failure, and fatal haemorrhage.4,5 Pulmonary and cerebral AVMs can occur in children, while hepatic complications increase with age.

HHT1 is associated with a higher prevalence of pulmonary and cerebral AVMs than HHT2.6 HHT1 is due to mutations in the Endoglin gene (ENG; MIM 131195),7 which codes for a homodimeric integral membrane glycoprotein expressed predominantly on the vascular endothelium. A total of 112 distinct ENG mutations distributed throughout the gene have been reported.8–11

Mutations in the ALK-1 gene (ACVRL1; MIM 601284), coding for an activin-like kinase receptor type I of the TGF-β superfamily predominantly expressed in endothelial cells,6,12–14 are responsible for HHT2. A total of 80 mutations of different types have been identified to date.10,11

The underlying mechanism of HHT1 (and probably HHT2) is haploinsufficiency, which implies that a reduction in the amount of protein to half normal levels predisposes to disease and that mutation type or position does not affect …

View Full Text


  • Conflict of interest: none declared.

  • * AK and MS contributed equally to this study.