Identification of an ND4 Mutation in Leber Hereditary Optic Neuropathy.

SIGNIFICANCE We identified a missense mutation, m.11778G>A (p.R340H), in the mitochondrially encoded NADH dehydrogenase 4 gene (ND4) in eight patients and three asymptomatic carriers, even though the incidence of this has been considered low in Chinese population. These results have implications for the families' genetic counseling and clinical management. PURPOSE Leber hereditary optic neuropathy (LHON OMIM 535000) is one of the most common inherited optic neuropathies. The aim of this study was to identify the genetic cause in two Han Chinese families with LHON. METHODS We used Sanger sequencing to identify the genetic cause of two Han Chinese families from Hunan, China, with LHON. RESULTS The patients in these two families presented with typical LHON, with male patients experiencing more severe phenotypes. A missense mutation, m.11778G>A (p.R340H), in the ND4 gene was identified in eight patients and three asymptomatic carriers, even though the incidence of this has been considered low in Chinese population. CONCLUSIONS Eight of 11 family members (72.7%) manifested some vision loss, which is far higher percentage than reported in other studies. The variant is predicted to be the disease-causing mutation and results in seriously abnormal function of complex I subunits of the mitochondrial respiratory chain. These results have implications for the families' genetic counseling and clinical management and help to develop new LHON target-gene therapy strategies.