[P1-145] Oxidative phosphorylation deficiency associated with two novel mitochondrial DNA mutations
[Objective] The aim of this study was to evaluate the contributions of two novel mutations of mitochondrial DNA (mtDNA) in oxidative phosphorylation (OXPHOS) deficiency. [Method] The complete mitochondrial genomes of seventy families with OXPHOS deficiency were screened for mutation analysis. Mitochondrial functional study was performed in primary and cybrid cells containing candidate mutations. [Result] Two novel mitochondrial DNA mutations, m.11240C>T in ND4 gene and m.12955A>G in ND5 gene, were identified from two OXPHOS defected patients with Leigh Syndrome. Both of the patients had mitochondrial complex I deficiency. The patient harboring m.12955A>G mutation had combined complex I and IV deficiencies. Their mitochondrial complexes defects were confirmed in transmitochondrial cybrid cells containing the mutations, suggesting that the m.11240C>T mutation might impair the proton pumping channel of complex I but had little effect on the complex I assembly. The m.12955A>G mutation probably impairs complex I assembly, resulting in reduced stability of complex IV. Further functional investigations revealed that mitochondria with the two mutations exhibited lower mitochondrial respiration. [Conclusion] We identified two novel mutations, m.11240C>T and 12955A>G in mitochondrial DNA, as mitochondrial disease-related mutations. Although nucleus DNA mutations are involved in the majority of OXPHOS defects, mitochondrial DNA mutations screening is important for the diagnosis of patients with mitochondrial disease.