Mitochondrial DNA variant M.4344T>C in tRNAGln causes developmental delay

Abstract

The current work discusses the identification of a novel pathogenic mitochondrial DNA variant, m.4344T>C, in tRNAGln and its implications for patients with developmental delay. The variant was identified in an 18-monthsold boy with developmental delay, and it was found to be heteroplasmic in the patient’s blood and oral epithelial cells. Functional studies demonstrated that the m.4344T>C variant impaired mitochondrial complexes I, III, and IV contents, resulting in defective mitochondrial respiration, elevated mitochondrial ROS production, reduced mitochondrial membrane potential, and decreased mitochondrial ATP levels compared to wild-type cybrids. This study expanded the genetic variant spectrum of mitochondrial diseases and provided a better understanding of the phenotypes associated with mitochondrial tRNAGln gene mutations, contributing to the clinical diagnosis of developmental delay in patients with mitochondrial DNA variants.