Generation of three human induced pluripotent stem cell lines, LUMCi024-A, LUMCi025-A, and LUMCi026-A, from two patients with combined oxidative phosphorylation deficiency 8 and a related control

Ruben W J van Helden; Matthew J Birket; Christian Freund; Christaan H Arendzen; Harald M Mikkers; Valeria Orlova; René I de Coo; Christine L Mummery; Milena Bellin

doi:10.1016/j.scr.2021.102374

Generation of three human induced pluripotent stem cell lines, LUMCi024-A, LUMCi025-A, and LUMCi026-A, from two patients with combined oxidative phosphorylation deficiency 8 and a related control

Stem Cell Res. 2021 May:53:102374. doi: 10.1016/j.scr.2021.102374. Epub 2021 Apr 29.

Authors

Ruben W J van Helden¹, Matthew J Birket¹, Christian Freund², Christaan H Arendzen², Harald M Mikkers³, Valeria Orlova¹, René I de Coo⁴, Christine L Mummery², Milena Bellin⁵

Affiliations

¹ Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands.
² Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands; Leiden University Medical Center hiPSC Hotel, Leiden, the Netherlands.
³ Leiden University Medical Center hiPSC Hotel, Leiden, the Netherlands.
⁴ Department of Neurology, Erasmus MC University Medical Centre, Rotterdam, the Netherlands; Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.
⁵ Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: [email protected].

PMID: 34088003
DOI: 10.1016/j.scr.2021.102374

Abstract

Combined Oxidative Phosphorylation Deficiency 8 (COXPD8) is an autosomal recessive disorder causing lethal childhood-onset hypertrophic cardiomyopathy. Homozygous or compound heterozygous mutations in the nuclear-encoded mitochondrial alanyl-tRNA synthetase 2 (AARS2) gene underly the pathology. We generated induced pluripotent stem cells (hiPSCs) from two patients carrying the heterozygous compound c.1774 C>T, c.2188 G>A and c.2872 C>T AARS2 mutations, as well as a related healthy control carrying the c.2872 C>T AARS2 mutation. All hiPSC-lines expressed pluripotency markers, maintained a normal karyotype, and differentiated towards the three germ layer derivatives in vitro. These lines can be used to model COXPD8 or mitochondrial dysfunction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cardiomyopathy, Hypertrophic*
Child
Heterozygote
Homozygote
Humans
Induced Pluripotent Stem Cells*
Mitochondrial Diseases*
Mutation