Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited ocular disease associated with mutations in the mitochondrial DNA (mtDNA). We describe the clinical and molecular genetic findings in a LHON patient and his family with a new mtDNA mutation at np14568 in the ND6 gene.
Methods: Ophthalmological examination was performed in one affected male and two maternal relatives. Direct sequence analysis of the complete mtDNA protein coding region was initiated in the affected patient. Four unaffected maternal relatives also underwent molecular genetic evaluation.
Results: Clinical examination of the affected male showed typical features of LHON. In his unaffected mother slight peripapillary microangiopathy was found. Molecular analysis did not show any of the common LHON mutations. A nucleotide exchange 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 members, but absent in 60 other LHON lineages and 175 unrelated controls.
Conclusion: The new mutation at nucleotide position 14568 lies in the close vicinity of other LHON-related mutations (np14459, np14484, np14498, np14596) within the evolutionarily most conserved region of the ND6 gene. Since no other mutation was detected throughout the mtDNA coding region and the new alteration was excluded in controls, our clinical and molecular genetic findings suggest that the novel point mutation at np14568 is responsible for LHON in this family.