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.