Purpose: Here we report a case of a patient with bilateral optic atrophy of unknown etiology carrying a novel de novo mutation in the OPA1 gene, which is a cause of autosomal dominant optic atrophy (DOA) and was detected in a whole-exome sequencing (WES) analysis of the patient without any family history of bilateral optic atrophy.
Case: A 7-year-old boy, who was found to have decreased visual acuity impairment in both eyes (BE) on preschool physical examination, visited our hospital. He was unaware of any visual impairment and had no family history of bilateral optic atrophy. His corrected visual acuity was 0.4 in the right eye (RE) and 0.5 in the left eye (LE). His anterior ocular segment and media were normal, and the fundus examination revealed optic disk pallor in BE. An optical coherence tomography scan revealed no structural abnormalities of the outer retinal layer in the macula; however, there was a significant decrease in the thickness of the macular inner retinal layers and circumpapillary retinal nerve fiber layer chickness. To elucidate the cause, the WES was performed on the trio samples (the patient and his parents). It demonstrated a novel heterozygous mutation (c. 2818+4A> G) in the donor splice site of intron 27. This mutation was identified to be de novo because the parents did not have the mutation. At the age of 18 years, the patient's corrected visual acuity was 0.2 in the RE and 0.1 in the LE, and the Goldmann visual field testing revealed a central scotoma in BE. The clinical features of the patient were consistent with those of DOA. In addition to slowly progressive visual impairment, myopic shift was observed during the 11 years of observation.
Conclusion: As the observed clinical findings were consistent with those of DOA, it is possible that a de novoOPA1 mutation can be detected by genetic testing of trio samples, although autosomal dominant inheritance is denied.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 126: 983-990,2022.