oligomycins and Syndrome

Mitochondrial (mt) DNA-associated NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) syndrome is due to mutation in the MT-ATP6 gene. We report the case of a 18-year-old man who presented with deafness, a myoclonic epilepsy, muscle weakness since the age of 10 and further developed a retinitis pigmentosa and ataxia. The whole mtDNA analysis by next-generation sequencing revealed the presence of the 2 bp microdeletion m.9127-9128 del AT in the ATP6 gene at 82% heteroplasmy in muscle and to a lower load in blood (10-20%) and fibroblasts (50%). Using the patient's fibroblasts, we demonstrated a 60% reduction of the oligomycin-sensitive ATPase hydrolytic activity, a 40% decrease in the ATP synthesis and determination of the mitochondrial membrane potential using the fluorescent probe tetramethylrhodamine, ethyl ester indicated a significant reduction in oligomycin sensitivity. In conclusion, we demonstrated that this novel AT deletion in the ATP6 gene is pathogenic and responsible for the NARP syndrome.

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Base Sequence; Carrier Proteins; Cells, Cultured; DNA Mutational Analysis; DNA, Mitochondrial; High-Throughput Nucleotide Sequencing; Humans; Male; Membrane Potential, Mitochondrial; Membrane Proteins; Mitochondrial Myopathies; Mitochondrial Proton-Translocating ATPases; Oligomycins; Retinitis Pigmentosa; Sequence Deletion; Syndrome; Young Adult