Generation of ENG p.Met1Val mutant LUMCi029-A-2 for modeling Hereditary Hemorrhagic Telangiectasia type 1.

Hereditary Hemorrhagic Telangiectasia type I (HHT1) is an autosomal dominant vascular disease caused by pathogenic variants in endoglin (ENG) gene. It is located on chromosome 9 and encodes for the Endoglin protein, which is involved in the TGFb/BMP signalling pathway. Using CRISPR/Cas9-mediated gene editing, the ENG c.1A > G mutation was introduced in homozygous form in the well-characterized LUMCi029-A line. The resulting hiPSC line, LUMCi029-A-2, showed typical morphology, expressed pluripotency markers, was able to differentiate into the three germ layers in vitro and displayed a normal karyotype. The line represents a valuable HHT1 disease-model and an important tool for drug testing.