Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia. Mutations in either ENG or ACVRL1 account for around 85% of cases and 10% are large deletions and duplications. Here we present a large novel deletion in ACVRL1 gene and its molecular characterization in a 3 generation Italian family. We employed short tandem repeats (STRs) analysis, direct sequencing, multiplex ligation-dependent probe amplification (MLPA) analysis, and ‘deletion-specific’ PCR methods. The deletion size is 4.594 bp and breakpoints in exon 3 and intron 8 show the presence of short direct repeats of 7 bp. We hypothesize, as causative molecular mechanism, the replication slippage model. Understanding the fine mechanisms associated with genomic rearrangements may indicate the nonrandomness of these events, highlighting hot spots regions. In this work we present also other studies related to molecular aspects of this disease. The analysis could help scientists to understand from the disease how molecular biology works to the exact genetic defect.