Genome sequencing reveals a deep intronic splicing ACVRL1 mutation hotspot in Hereditary Haemorrhagic Telangiectasia

INTRODUCTION: Yet the genetic cause remains unknown for some families even after exhaustive exome analysis. We hypothesised that non-coding regions of the known HHT genes may harbour variants that disrupt splicing in these cases. METHODS: . Individuals from both groups had tested negative previously for a mutation in the coding region of known HHT genes. Samples were sequenced on a HiSeq2500 instrument and data were analysed to identify novel and rare variants. RESULTS: intron 9 that disrupted splicing. CONCLUSIONS: intron 9. The addition of this region to HHT molecular diagnostic testing algorithms will improve clinical sensitivity.