MITOCHONDRIAL-DNA MUTATIONS IN CUBAN OPTIC AND PERIPHERAL NEUROPATHY

Objective: To investigate the potential role of mito-chondrial DNA (mt DNA) 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 ass ociated 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 p atients harbored any of the 8 other LHON-associated mtDNA mutations. D etailed sequence analysis revealed that the Cuban patients could be di vided into 7 distinct mtDNA haplotypes and that the 2 COPN patients wi th mtDNA mutations in the cytochrome c oxidase subunit III gene were n ot 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 mutati ons may play a role in some cases. mtDNA mutations may render an indiv idual genetically susceptible to a variety of factors that impair oxid ative phosphorylation, including nutritional deficiency, tobacco, alco hol, and other toxins.