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
Summary
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 |