MT-ND4 and Leber hereditary optic neuropathy: The LHON pathogenic mutations do not express a similar pathogenic potential: the severity of the biochemical defect in LHON shows a clear gradient from the 3460/ND1 (most severe), to the 14484/ND6 (mildest), passing through the intermediate features of the 11778/ND4 mutation.2 The 3640/ND1 mutation is the most penetrant when homoplasmic, presents with less gender difference and has a very low rate of visual recovery.