Generation and heterozygous repair of human iPSC lines from three individuals with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) carrying biallelic AAGGG expansions in RFC1

Kayli C Davies; Kiymet Bozaoglu; Paul J Lockhart

doi:10.1016/j.scr.2023.103047

Generation and heterozygous repair of human iPSC lines from three individuals with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) carrying biallelic AAGGG expansions in RFC1

Stem Cell Res. 2023 Apr:68:103047. doi: 10.1016/j.scr.2023.103047. Epub 2023 Feb 14.

Authors

Kayli C Davies¹, Kiymet Bozaoglu¹, Paul J Lockhart²

Affiliations

¹ Murdoch Children's Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
² Murdoch Children's Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia. Electronic address: [email protected].

PMID: 36805468
DOI: 10.1016/j.scr.2023.103047

Abstract

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a progressive neurodegenerative disorder predominantly caused by biallelic AAGGG expansions in the second intron of the RFC1 gene. Here, we used a simultaneous reprogramming and CRISPR-Cas9 genome editing approach to generate three patient iPSC lines with homozygous AAGGG expansions along with three heterozygous gene corrected iPSC lines. The iPSC lines expressed pluripotency markers, had a normal karyotype, and were able to differentiate into all three embryonic germ layers. These mutant and corrected iPSC lines will be a valuable tool for studying the molecular mechanisms underlying CANVAS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bilateral Vestibulopathy*
Cerebellar Ataxia* / genetics
Heterozygote
Humans
Induced Pluripotent Stem Cells*
Peripheral Nervous System Diseases*
Syndrome