Background  Inherited optic neuropathy (ION) is often classified as unexplained optic nerve atrophy. Genetic testing helps to clarify the cause of optic nerve atrophy.

  Objective  To analyze the diversity of mutant genes and clinical phenotypes in patients with optic atrophy in one single-center, so as to provide theoretical reference for guiding the diagnosis and treatment of ION.

  Methods  The patients diagnosed with suspected optic atrophy in the Department of Ophthalmology, Chinese PLA General Hospital were enrolled for molecular genetic testing from January 1, 2017 to August 31, 2021. The mutation genes related to optic atrophy were analyzed and summarized.

  Results  Of the 479 patients, 260 patients were diagnosed with ION, and the positive rate of gene mutation was 54.3% (260/479). In the patients with ION, 80.3% (209/260) of them had 28 types of mitochondrial gene (mtDNA) mutation sites, and 19.7% (51/260) of them had 15 types of nuclear gene (nDNA) mutations. Among the patients with mtDNA mutations, 97.6% (204/209) of them were diagnosed with Leber hereditary optic neuropathy (LHON), these patients were young (20.79 ± 11.44 years), mostly were male (84.8%, 173/204), and nearly one-third (32.3%, 66/204) of the patients had family histories, 76.5% (156/204) of the LHON patients carried common mutation sites, 17.6% (36/204) of them carried rare mutation sites, and 5.9% (12/204) of them had two mutation sites. In addition, 3 cases of Leigh syndrome were related to m.13513G ＞ A mutation, 1 case of MELAS syndrome was related to m.12264C ＞ T, and 1 case of MERRF syndrome was described to m.13042G ＞ A. Among the 51 patients with nuclear gene mutation, 24 patients were detected with OPA1 gene related to dominant optic atrophy (DOA), and 6 patients were detected with OPA3 gene mutation. In these 24 patients with OPA1 gene mutation, 17 cases were male, with an average age of (20.78 ± 17.00) years, and 5 cases had family histories. Among the patients with non-DOA related nuclear gene mutations, 5 cases of Wolfram syndrome were associated with WFS1 mutations, 3 cases of chronic progressive extraocular muscle palsy were related to RRM2B mutations, 13 cases of optic nerve atrophy were related to other rare mutated nDNA.

  Conclusion  The genetic types and clinical phenotypes of hereditary optic atrophy are diverse. LHON and DOA are the leading causes of optic nerve atrophy in ION. It’s necessary to pay attention to the rare mtDNA mutation of LHON and clinical phenotypes with other nuclear gene mutations except for OPA1 and OPA3, which will help improve the diagnosis rate of ION.