Genome editing of a low-penetrance albinism-associated variant in TYR in patient-derived pluripotent stem cells

Summary

TYR encodes tyrosinase, the enzyme catalysing the initial steps of melanin biosynthesis in melanocytes and retinal pigment epithelia (RPE). TYR c.1205G>A (p.Arg402Gln) is a common genetic variant associated with several pigmentation traits. Notably, when this variant is encountered in specific haplotypic backgrounds in the homozygous state, it predisposes to albinism. We generated an induced pluripotent stem cell (iPSC) line from an affected individual carrying such a homozygous genotype (UMANi255-A), and then used CRISPR-Cas9 to correct the TYR c.1205G>A variant (UMANi255-A-1). The resulting iPSC lines demonstrate capacity for multi-lineage differentiation, providing a useful in vitro model for studying pigmentation biology. Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.

Authors Downton P, Bates N, Woods S, Adamson A, Sergouniotis PI
Journal Stem cell research
Publication Date 2025 Dec;89:103855
PubMed 41308567
DOI 10.1016/j.scr.2025.103855

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