Work

Developing iPSC models from phenylketonuria patients with varying PAH gene mutations

Year: 2025

Type: article

Abstract: Phenylketonuria (PKU), a common autosomal recessive metabolic disorder, arises from diverse pathogenic variants in the phenylalanine hydroxylase (PAH) gene, causing phenylalanine accumulation and neurological impairment. The vast spectrum of over 2,200 PAH variants and frequent compound heterozygosity complicate genotype-phenotype prediction, highlighting the need for deeper mechanistic insight. We generated human induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells of four PKU patients with distinct PAH genotypes using non-integrating Sendai viruses. The iPSC lines were validated for pluripotency, vector clearance, and genomic integrity. These patient-specific iPSCs provide a valuable platform for elucidating PKU pathophysiology and advancing personalized therapeutic development.

Source: Stem Cell Research

DOI: 10.1016/j.scr.2025.103885

Authors: Desi Veleva, Mohammad M. Chowdhury, Merve Ay, Andrew B.J. Prowse, Michael Nafisinia

Institutions: The University of Queensland, The University of Sydney, Westmead Institute for Medical Research

Language: English

Topic: Pluripotent Stem Cells Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,360