SMAD4 and hereditary hemorrhagic telangiectasia: The classical Sanger sequencing analysis of genes, including genes found as the main cause for HHT, ENG and ACVRL1/ALK1 and sometimes MADH4/SMAD4 (Figures 2A,B) is currently the method followed in most genetic diagnosis laboratories, complemented with the MLPA (multiplex ligation-dependent probe amplification) technique for large deletion/insertions of exons.