Mitochondrial DNA Mutations in Cuban Optic and Peripheral Neuropathy

OBJECTIVE: To investigate the potential role of mitochondrial DNA (mtDNA) mutations in the recent outbreak in Cuba of optic neuropathy and peripheral neuropathy (COPN). DESIGN AND METHODS: Historical features were reviewed and neuro-ophthalmologic examinations were performed on a sample of COPN patients (n = 9) and Cuban patients with other forms of optic neuropathy (n = 2). Molecular genetic methods were then used to test for the presence of 9 mtDNA mutations that were previously associated with Leber's hereditary optic neuropathy (LHON). RESULTS: Two (22%) of 9 COPN patients harbored an LHON-associated mtDNA mutation at nucleotide position 9438 and a novel mutation at nucleotide position 9738 in the cytochrome c oxidase subunit III gene. None of the Cuban patients harbored any of the 8 other LHON-associated mtDNA mutations. Detailed sequence analysis revealed that the Cuban patients could be divided into 7 distinct mtDNA haplotypes and that the 2 COPN patients with mtDNA mutations in the cytochrome c oxidase subunit III gene were not members of the same maternal lineage. CONCLUSIONS: The pathogenesis of epidemic COPN is likely complex and multifactorial. Our preliminary results in a small sample of Cuban patients suggest that mtDNA mutations may play a role in some cases. mtDNA mutations may render an individual genetically susceptible to a variety of factors that impair oxidative phosphorylation, including nutritional deficiency, tobacco, alcohol, and other toxins.