G.P.3.13 Supplementation studies in primary human muscle cells with mtDNA depletion caused by mutations in the DGUOK and POLG1 genes

Abstract

Mitochondrial DNA depletion syndrome (MDS), a frequent cause of severe childhood (hepato)encephalomyopathies, is defined as a reduction of mitochondrial DNA copy number related to nuclear DNA in different tissues which leads to insufficient synthesis of respiratory chain complexes. Mutations of eight nuclear genes (DGUOK, POLG1, MVP17. ECGF1, TK2, SUCLA2, SUCLG1 and RRM2B), all involved in the synthesis or maintenance of mitochondrial nucleotide pools, were identified. It was previously shown that mtDNA depletion can be prevented by dGMP and dAMP supplementation in culture of deoxyguanosine kinase-deficient fibroblasts.