Abstract: Objective To report the results of mutation analysis of the OPA1 gene in a cohort of patients with suspected hereditary optic atrophy and describe clinical features of autosomal dominant optic atrophy (ADOA) patients. Design Retrospective case series. Participants Two hundred and ninety-one suspected ADOA probands who have been excluded from 16 primary mitochondrial DNA mutations associated with Leber hereditary optic neuropathy (LHON) in our prior screening. Among them 55 had a family history of hereditary optic neuropathy, and 236 were sporadic cases. All patients were unrelated. Methods The coding region (exon 1-28), including intron-exon boundary of the OPA1 gene, were screened in participants and some family members by using PCR-based sequencing methods. The clinical features of ADOA patients were recorded. Main Outcome Measures Mutations of OPA1 gene, family history, age of onset, visual acuity, and fundus photography. Results Fifty-one OPA1 pathogenic mutations were found in 60 patients (60/291, 20.6%). Of the 51 intragenic mutations, 37 were detected for the first time in this study or in our precious studies. The mutations contained 43% (22/51) of missense mutations, 19% (10/51) of nonsense mutations, 14% (7/51) of splice site mutations, and 24% (12/51) of deletions or insertions. The majority of OPA1 intragenic mutations were located in exon 27 and 9, for 8 and 6 times, respectively. Followed by exon 8, 26 and 28, where mutations had been identified 5 times. One reported mutation c.2708_2711delTTAG in exon 27 was identified in 6 unrelated probands. The male-to-female ratio of the 60 positive probands was almost 1.4:1. The mean onset age of visual deficit was 7.97±7.31 years (ranging from 3-33 years) and the mean logMAR visual acuity for the probands carrying OPA1 mutations was 0.84±0.42. Sixty ADOA patients presented with bilateral, symmetric visual failure and optic nerve degeneration. In this study, the appearance of the optic nerve head was divided into two categories, with a prominent temporal wedge pallor in 45 of 60 patients (75%) and total disc pallor observed in 13 of 60 patients (22%). Conclusion Our findings expand the spectrum of OPA1 mutation and the exon 8, 9 and 26 to 28 were the hot regions of OPA1 gene mutations. It is important to perform an OPA1 gene mutation analysis for patients with suspected autosomal dominant optic atrophy. (Ophthalmol CHN, 2015, 24: 79-84)

Key words: autosomal dominant optic atrophy(ADOA), OPA1 mutations