Research article
Mutation study of Spanish patients with Hereditary Hemorrhagic Telangiectasia
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* Corresponding author: Luisa M Botella cibluisa@cib.csic.es
1 Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu, 9. Madrid 28040, Spain
2 Departamento de Genetica Medica. Hospital Marques de Valdecilla. Santander. Spain
3 Departamento de Medicina Interna, Hospital Sierrallana, Torrelavega, Santander, Spain
4 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
BMC Medical Genetics 2008, 9:75 doi:10.1186/1471-2350-9-75
Published: 1 August 2008Abstract
Background
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant and age-dependent vascular disorder characterised mainly by mutations in the Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes.
Methods
Here, we have identified 22 ALK1 mutations and 15 ENG mutations, many of which had not previously been reported, in independent Spanish families afflicted with HHT.
Results
We identified mutations in thirty-seven unrelated families. A detailed analysis of clinical symptoms was recorded for each patient analyzed, with a higher significant presence of pulmonary arteriovenous malformations (PAVM) in HHT1 patients over HHT2. Twenty-two mutations in ALK1 and fifteen in ENG genes were identified. Many of them, almost half, represented new mutations in ALK1 and in ENG. Missense mutations in ENG and ALK1 were localized in a tridimensional protein structure model.
Conclusion
Overall, ALK1 mutations (HHT2) were predominant over ENG mutations (HHT1) in our Spanish population, in agreement with previous data from our country and other Mediterranean countries (France, Italy), but different to Northern Europe or North America. There was a significant increase of PAVM associated with HHT1 over HHT2 in these families.