Generation and genetic repair of 2 iPSC clones from a patient bearing a heterozygous c.1120del18 mutation in the ACVRL1 gene leading to Hereditary Hemorrhagic Telangiectasia (HHT) type 2


Fibroblasts from a patient carrying a heterozygous 18bp deletion in exon 8 of the ACVRL1 gene (c.1120del18) were reprogrammed using episomal vectors. The in-frame deletion in ACVRL1 causes the loss of 6 amino acids of the protein, which is associated with Hereditary Hemorrhagic Telangiectasia (HHT) type 2 (Letteboer et al., 2005). CRISPR-Cas9 editing was used to genetically correct the mutation in the induced pluripotent stem cells (iPSCs). The top5-predicted off-target sites were not altered. Patient and isogenic iPSCs showed high pluripotent marker expression, in vitro differentiation capacity into all three germ layers and displayed a normal karyotype. The obtained isogenic pairs will enable proper in vitro disease modelling of HHT (Roman and Hinck, 2017). Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Authors Bouma MJ, Orlova V, van den Hil FE, Mager HJ, Baas F, de Knijff P, Mummery CL, Mikkers H, Freund C
Journal Stem cell research
Publication Date 2020 Jul;46:101786
PubMed 32485642
DOI 10.1016/j.scr.2020.101786

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