SMAD4 and hereditary hemorrhagic telangiectasia: These loci include the HHT3 locus on chromosome 5 or the HHT4 locus on chromosome 7, whose genes remain unidentified (Cole et al., 2005; Bayrak-Toydemir et al., 2006), along with mutations in the MADH4/SMAD4 gene causing familial juvenile polyposis associated with HHT (Gallione et al., 2004).