De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans

Defects in the mitochondrial genome (mitochondrial DNA (mtDNA)) are associated with both congenital and acquired disorders in humans. Nuclear-encoded DNA polymerase subunit gamma ( ) plays an important role in mtDNA replication, and proofreading and mutations in have been linked with increased mtDNA deletions. is also a crucial gene for mtDNA replication. Here, we describe a patient diagnosed with Pearson syndrome with large mtDNA deletions that were not detected in the somatic cells of the mother. Exome sequencing was used to evaluate the nuclear factors associated with the patient and his family, which revealed a paternal mutation (c.868C > T) and a maternal mutation (c.320G > A). The patient showed lower and expression than his healthy brothers and the general population of a similar age. Notably, c.868C in the wild-type allele was highly methylated in the patient compared to the same site in both his healthy brothers. These results suggest that the co- deficient expression of and genes could contribute to the development of mtDNA deletion.