Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in either the TSC1 or TSC2 genes. Though TSC causes the formation of nonmalignant tumors throughout multiple organs, the most frequent causes of mortality and morbidity are due to neurological complications. In two-thirds of cases, TSC occurs sporadically and TSC2 pathogenic variants are approximately three times more prevalent than TSC1 pathogenic variants. Here, we utilized CRISPR-Cas9-mediated homology directed repair in patient induced pluripotent stem cells (iPSCs) to correct two types of TSC2 pathogenic variants generating two isogenic lines. In one line, we corrected a splice acceptor variant (c.2743-1G>A), which causes the skipping of coding exon 23 and subsequent frameshift and introduction of a stop codon in coding exon 25. In the second line, we corrected a missense variant in coding exon 40 within the GTPase-activating protein domain (c.5228G>A, p.R1743Q). The generation of TSC2 patient iPSCs in parallel with their corresponding CRISPR-corrected isogenic lines will be an important tool for disease modeling applications and for developing therapeutics.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.