Unusual adult-onset Leigh syndrome presentation due to the mitochondrial m.9176T>C mutation

► Leigh syndrome (LS) is an incurable neurodegenerative pediatric disorder that results from respiratory chain failure. ► LS is associated with mutations in ATP6 and ATP8 mitochondrial genes (mtDNA). ► We describe clinical and molecular features of a young woman with an unusual adult-onset LS while her brother died at a young age. ► The homoplasmic m.9176T→C mutation was found in her muscle-extracted mtDNA. ► This novel case report and literature review highlights the variability of phenotypic expression of the m.9176T→C mutation. Leigh syndrome (LS) is an incurable, nearly always fatal, neurodegenerative, pediatric disorder that results from respiratory chain failure. The most common mitochondrial DNA (mtDNA) mutations that result in LS are m.8993T→C/G and m.9176T→C/G, which were previously found in several patients with early-onset Leigh syndrome. Here, we describe clinical and molecular features of a novel pedigree, where LS developed in two siblings. The proband was a young woman with an unusual adult-onset LS. She harbored a homoplasmic m.9176T→C mutation, based on analysis of a muscle biopsy. In contrast, the brother died at a young age. This novel case report and literature review highlights the variability of phenotypic expression of the m.9176T→C mutation.