Generation of induced pluripotent stem cells (UCLi024-A) from a patient with argininosuccinate lyase deficiency carrying a homozygous c.437G > A (p.Arg146Gln) mutation

Claire Duff; Madeha Islam; Onelia Gagliano; Hema Pramod; Hassan Rashidi; Manju A Kurian; Paul Gissen; Julien Baruteau

doi:10.1016/j.scr.2024.103365

Generation of induced pluripotent stem cells (UCLi024-A) from a patient with argininosuccinate lyase deficiency carrying a homozygous c.437G > A (p.Arg146Gln) mutation

Stem Cell Res. 2024 Apr:76:103365. doi: 10.1016/j.scr.2024.103365. Epub 2024 Feb 28.

Authors

Claire Duff¹, Madeha Islam², Onelia Gagliano³, Hema Pramod⁴, Hassan Rashidi², Manju A Kurian⁴, Paul Gissen⁵, Julien Baruteau⁵

Affiliations

¹ Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK. Electronic address: claire.duff@ucl.ac.uk.
² Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
³ Onyel Biotech S.r.l., Padova, PD, Italy; Department of Industrial Engineering, University of Padova, Padova, Italy; Veneto Institute of Molecular Medicine, Padova, Italy.
⁴ Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK; National Institute of Health Research, Great Ormond Street Biomedical Research Centre, London WC1N 1EH, UK.
⁵ Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK; National Institute of Health Research, Great Ormond Street Biomedical Research Centre, London WC1N 1EH, UK; Metabolic Medicine Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.

PMID: 38422816
DOI: 10.1016/j.scr.2024.103365

Abstract

Argininosuccinic aciduria (ASA) is a rare inherited metabolic disease caused by argininosuccinate lyase (ASL) deficiency. Patients with ASA present with hyperammonaemia due to an impaired urea cycle pathway in the liver, and systemic disease with epileptic encephalopathy, chronic liver disease, and arterial hypertension. A human induced pluripotent stem cell (iPSC) line from the fibroblasts of a patient with ASA with homozygous pathogenic c.437G > A mutation of hASL was generated. Characterization of the cell line demonstrated pluripotency, differentiation potential and normal karyotype. This cell line, called UCLi024-A, can be utilized for in vitro disease modelling of ASA, and design of novel therapeutics.

MeSH terms

Argininosuccinate Lyase / genetics
Argininosuccinic Aciduria* / genetics
Argininosuccinic Aciduria* / metabolism
Argininosuccinic Aciduria* / therapy
Homozygote
Humans
Induced Pluripotent Stem Cells* / metabolism
Mutation / genetics

Substances

Argininosuccinate Lyase