Universitą degli studi di Pavia

As part of my PhD program in "Pathology and Medical Genetics", I am working on the mutational study of a genetically determined disease: Hereditary haemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu syndrome, is inherited as an autosomal dominant trait. It affects approximately 1 in 5000 individuals with regional differences and isolated communities displaying higher prevalences due to founder effects. HHT is described as a familial disease characterised by severe recurrent nasal and gastrointestinal bleeding with associated anaemia and telangiectasia on the lips and finger tips. The majority of HHT patients are also affected by larger arteriovenous malformations (AVMs) in the pulmonary, hepatic, cerebral and other circulations. These features are used as criteria to diagnose HHT (Curaēao criteria). Three of the genes mutated in HHT have been identified: ENG on chromosome 9q34.1 (resulting in HHT1, OMIM #187300); ACRVL1 on chromosome 12q11-q14 (resulting in HHT2, OMIM#600376) and more rarely, SMAD4 on chromosome 18q21.1 (mutated in HHT in association with juvenile polyposis, JPHT, OMIM #175050).
Our work is based on the mutation analysis of ENG and ACVRL1 genes, the genotype phenotype correlation, the distribution of TGFbeta polymorphisms and significance on disease severity, and the analysis of the relevance of different ACVRL1 mutations on the protein structure.