MT-ND4 and Leber hereditary optic neuropathy: SIFT and PolyPhen analysis of all nonsynonymous changes from cases and controls revealed five pathogenic changes, including primary LHON mutations (p.A52T in ND1 protein; p.M64V in ND6; p.M181T in adenosine triphosphate (ATP) synthase subunit a (F-ATPase protein 6) [ATPase6]; p.R340H in ND4, and p.F181L in cytochrome B (CYB) protein; Table 2 and Table 3).