Leber's hereditary optic neuropathy: clinical and molecular genetic findings in a patient with a new mutation in the ND6 gene

Background: Leber's hereditary optic neuropathy (LHON) is a maternally inhe rited ocular disease associated with mutations in the mitochondrial DNA (mt DNA). We describe the clinical and molecular genetic findings in a LHON pat ient and his family with a new mtDNA mutation at np14568 in the ND6 gene, M ethods: Ophthalmological examination was performed in one affected male and two maternal relatives. Direct sequence analysis of the complete mtDNA pro tein coding region was initiated in the affected patient. Four unaffected m aternal relatives also underwent molecular genetic evaluation. Results: Cli nical examination of the affected male showed typical features of LHON. In his unaffected mother slight peripapillary microangiopathy was found. Molec ular analysis did not show any of the common LHON mutations. A nucleotide e xchange was detected at position 14568 replacing a glycine by serine in the ND6 gene. This mutation was the only new mutation found within the entire protein and tRNA coding region of the patient's mitochondrial genome. This novel mutation was also present in four non-affected maternal family member s, but absent in 60 other LHON lineages and 175 unrelated controls. Conclus ion: The new mutation at nucleotide position 14568 lies in the close vicini ty of other LHON-related mutations (np14459, np14484, np14498, np14596) wit hin the evolutionarily most conserved region of the ND6 gene. Since no othe r mutation was detected throughout the mtDNA coding region and the new alte ration was excluded in controls, our clinical and molecular genetic finding s suggest that the novel point mutation at np14568 is responsible for LHON in this family.