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

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.