Hereditary haemorrhagic telangiectasia (HHT) is diagnosed clinically by the Curacao Criteria of spontaneous recurrent nosebleeds, mucocutaneous telangiectasia at characteristic sites, visceral involvement (arteriovenous malformations (AVMs); gastrointestinal telangiectasia) and family history.1 Early diagnosis is important to enable AVM screening and preventative treatments.2–5 HHT is caused by loss-of-function DNA variants in ENG, ACVRL1, SMAD4 or GDF2,6–9 though older manuscripts describing linkage to additional loci10 11 continue to be referenced heavily. In whole genome sequencing (WGS) performed prospectively for HHT ‘gene-negative’ patients recruited to the National Health Service (NHS) 100 000 Genomes Project,12 no candidate variants were identified in the HHT3 or HHT4 loci. ‘HHT gene-negative’ families receiving a clinical positive test result included the original HHT3 family, and a family diagnosed with a related vasculopathy (capillary malformation…
