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SMAD4 mutations found in unselected HHT patients.
C J Gallione1, J A Richards, T G W Letteboer
1Duke University Medical Center, Durham, NC 27710, USA.
Journal of Medical Genetics
|April 15, 2006
Summary
Hereditary haemorrhagic telangiectasia (HHT) patients negative for ENG and ALK1 mutations may have SMAD4 mutations. This finding suggests these HHT patients are at risk for juvenile polyposis (JP)-HHT and associated gastrointestinal cancer risks.
Area of Science:
- Genetics
- Molecular Biology
- Medical Genetics
Background:
- Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder.
- Mutations in endoglin (ENG) and activin receptor-like kinase 1 (ALK1) genes are common causes of HHT.
- SMAD4 mutations are associated with the combined juvenile polyposis (JP) and HHT (JP-HHT) syndrome.
Purpose of the Study:
- To investigate the prevalence of SMAD4 mutations in HHT patients without a prior JP diagnosis.
- To assess the clinical implications of identifying SMAD4 mutations in this HHT cohort.
Main Methods:
- Genetic analysis of 30 unrelated HHT patients negative for ENG and ALK1 mutations.
- DNA-based testing for mutations in the SMAD4 gene.
Main Results:
- SMAD4 mutations were identified in 10% (3/30) of the tested HHT patients.
- The identified SMAD4 mutations were consistent with those observed in JP-HHT syndrome.
Conclusions:
- SMAD4 mutation screening should be considered in HHT patients with negative ENG and ALK1 results.
- Patients with SMAD4 mutations require screening for JP-associated polyps due to increased gastrointestinal cancer risk.