Using whole-exome sequencing, we screened for variants in unrelated patients presenting inherited optic neuropathies (ION) with a negative molecular diagnosis after analyzing OPA1, OPA3, WFS1, SPG7, AFG3L2, DNM1L, MFN2 exonic sequences, and pathogenic variants in the mitochondrial DNA responsible for LHON. Here, AFG3L2 is linked to Leber hereditary optic neuropathy.