Generation and characterization of induced pluripotent stem cells from a patient with classic Fabry disease

Abstract

Fabry disease is an X-linked lysosomal storage disorder caused by pathogenic variants in the α-galactosidase A (α-Gal A, GLA) gene. The disease exhibits substantial clinical heterogeneity, with renal injury representing one of its most prominent manifestations. Due to the scarcity of human renal specimens and the inability of conventional animal models to recreate patient-specific pathological features, the precise mechanism underlying renal-predominant Fabry disease remains poorly understood. In this study, we successfully established and comprehensively characterized a urine-derived induced pluripotent stem cell (iPSC) line from a 35-year-old male patient with classic Fabry disease with a typical renal-dominant phenotype. The patient carried the GLA c.1080_1082delTGG (p.Gly361del) variant. Non-integrating episomal reprogramming was used to generate monoclonal iPSCs, which were further validated for pluripotency, trilineage differentiation ability, genomic stability, and exogenous vector clearance. The established iPSC line stably retained the patient-specific pathogenic variant, exhibited full pluripotent properties, and showed no genomic abnormality or residual episomal integration. Therefore, this well-characterized renal-phenotype-specific iPSC line provides a reliable cellular platform for investigating the mechanisms of progressive Fabry disease nephropathy and can facilitate future targeted drug screening.