Generation of patient-derived and gene-corrected hiPSC lines from Hereditary Hemorrhagic Telangiectasia type 2 patients with ACVRL1 c.1042delG mutation

Abstract

Hereditary Hemorrhagic Telangiectasia type 2 (HHT2) is a vascular disorder caused by mutations in ACVRL1. We generated human induced pluripotent stem cell (hiPSC) lines from two HHT2 patients with a heterozygous 1 bp deletion in exon 7 of ACVRL1 (c.1042delG) by reprogramming skin fibroblasts. Gene-corrected isogenic hiPSCs were created using CRISPR-Cas9. All lines displayed normal karyotypes, expressed markers of the undifferentiated state, differentiated into all germ layers in vitro, and showed no off-target effects. These patient-derived, genetically matched hiPSC pairs provide a robust platform for modeling HHT2 in vitro and investigating molecular mechanisms of pathogenesis.