Establishment of human induced pluripotent stem cell lines and isogenic gene-corrected controls from three patients with prolidase deficiency

Summary

Prolidase deficiency is an autosomal recessive inborn error of metabolism caused by pathogenic variants in the PEPD gene. To date, close to 200 patients have been reported worldwide with a poorly understood pathomechanism. The PEPD gene encodes an enzyme that is involved in the final steps of collagen degradation. Urine amino acid analysis or specific dipeptide analysis can establish the biochemical diagnosis. In this study, we reprogrammed peripheral blood mononuclear cells (PBMCs) from three prolidase deficient patients into induced pluripotent stem cell (iPSC) lines and additionally generated isogenic controls using CRISPR-Cas9 genome editing. The pathogenic PEPD variants identified in our patients were NP_000276.2:p.? (NIHTVBi032-A), NP_000276.2:p.(Ile415Asn)/NP_000276.2:p.(Trp326Ter) (NIHTVBi033-A), and NP_000276.2:p.(Arg265Ter) (NIHTVBi034-A). These iPSC lines are valuable models to help investigate the pathomechanism of prolidase deficiency. Published by Elsevier B.V.

Authors Suri R, Emmerich K, Manohar-Sindhu S, MacCall E, Harper RL, Schwartzbeck R, Huffstutler R, Ferrante E, Tang X, Yang D, Dmitrieva NI, Lin Y, Zou J, Ferreira CR, Aksentijevich I, Freeman AF, Brofferio A, Cudrici C, Boehm M
Journal Stem cell research
Publication Date 2026 Sep;95:104091
PubMed 42673728
DOI 10.1016/j.scr.2026.104091

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