Molecular defects in rare bleeding disorders: hereditary haemorrhagic telangiectasia.
Vascular diseases may mimic coagulopathies by presenting as a haemorrhagic state. The archetypal example of an inherited disorder resulting in haemorrhage from dilated vessels of the microvasculature (telangiectasia) is Hereditary Haemorrhagic Telangiectasia (HHT, Rendu-Osler-Weber syndrome). This autosomal dominant disorder is characterised by haemorrhage from nasal, mucocutaneous and gastrointestinal telangiectasia, in addition to vascular anomalies in other organs, particularly in the pulmonary, hepatic and cerebral circulations. Linkage analyses have indicated there are at least three HHT loci, including the genes for endoglin on chromosome 9, and activin-like receptor kinase (ALK1) on chromosome 12. Mutations in these genes, together with recent data on the normal function of the encoded proteins highlight the role of TGF-b family members in the pathogenesis of HHT. Complimentary information from other telangiectatic states indicates potential precipitants, and indicate a critical role for TGF-beta ligand-receptor interactions in vascular homeostasis.
Shovlin
C L
CL
Department of Genetics, Harvard Medical School, Boston, MA, USA.
D029404:Activin Receptors; D015703:Antigens, CD; D002874:Chromosome Mapping; D000071063:Endoglin; D005838:Genotype; D006801:Humans; D010641:Phenotype; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics* / Q000503:physiopathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors