The mitochondrial ND5 T12338C mutation may influence the phenotypic manifestation of Leber’s hereditary optic neuropathy-associated ND4 G11696A mutation

Mutations in mitochondrial genome are the important causes of Leber’s Hereditary Optic Neuropathy (LHON). To investigate the pathophysiology of LHON, we recently initiated a systematic mutational screening for the candidate pathogenic mutations in mitochondrial genome. In this study, we described a Chinese family with LHON. Four of nine matrilineal relatives exhibited variable degree of vision loss, as well as different age at onset of LHON. Sequence analysis of the complete mitochondrial genome of the proband and the matrilineal relatives showed the presence of ND4 G11696A (Val to Ile) and ND5 T12338C (Met to Thr) mutations, as well as a set of polymorphisms belonging to human mitochondrial haplogroup F2. Of these, the G11696A was a primary mutation associated LHON and reported to modulate the clinical expression of deafness-associated A1555G mutation, in addition, the T12338C mutation was known to decrease the ND5 mRNA level and to inhibit the processing of RNA precursors. Thus, the T12338C mutation, acted a modified factor, may increase the clinical expression of LHON-associated ND4 G11696A mutation in this Chinese family.