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Modeling hereditary distal renal tubular acidosis using patient-derived iPSCs with WDR72 mutations

ABSTRACT: Distal renal tubular acidosis (dRTA) is a rare genetic disorder characterized by impaired urine acidification. The WDR72 gene has recently been implicated in dRTA, though its precise functional mechanisms remain unclear. In this study, we generated induced pluripotent stem cell (iPSC) from a patient with WDR72 mutations to model the disease. Upon differentiation into renal tubular epithelial cells, the wild-type and mutant cells (variants c.1777A>G and c.2522T>A) were analyzed for RNA expression, protein localization, and H+-ATPase trafficking. The results indicated no significant changes in these parameters, with the mutant protein retaining its role in acid-base homeostasis. Transcriptomic analysis revealed the top 10 differentially expressed genes (DEGs) were predominantly associated with the collagen-containing extracellular matrix, suggesting a potential link between WDR72 function and extracellular matrix composition. These findings highlight the value of iPSC-derived cellular models in advancing personalized research on dRTA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE305256 | GEO | 2025/08/28

REPOSITORIES: GEO

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