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SHIGERU SATO, Noriyasu Hashida, Takeshi Morimoto, Kikuko Hotta, Takashi Fujikado, Kohji Nishida; Novel OPA1 gene mutations in Japanese patients with optic atrophy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):410.
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© ARVO (1962-2015); The Authors (2016-present)
Dominant optic atrophy (DOA) is the most common form of hereditary optic neuropathy, and 4 causative genes had been registered in RetNetTM database. Among them, OPA1 gene is major causative gene. To date, 132 pathogenic or likely pathogenic variants of OPA1 were registered in ClinVar database. Here we report two novel potentially pathogenic variants in OPA1 gene in Japanese patients.
We conducted whole exome sequencing(WES) on 5 unrelated Japanese patients (4 males and 1 female) with bilateral optic atrophy who gave a written consent for genetic testing. All participants underwent complete ophthalmic examinations, including best-corrected visual acuity(BCVA) measurements, fundus photography, and optical coherence tomography(OCT). For sequencing, Illumina's Hiseq 2500 Platform was used. Sequence reads were aligned to the reference human genome (UCSC hg19). After cleaning and filtering the sequence data, we checked variants of the known causative genes of optic atrophy, which include AFG3L2, MFN2, NR2F1, OPA1, ACO2, NBAS,RTN4IP1, SLC25A46, TMEM126A, TIMM8A. Novel variants of OPA1 were validated by PCR direct sequence with Sanger’s method.
Case1 was a 23-year-old female. She complained of bilateral visual disturbance. No general or ophthalmic medical history should be noted, but her father and granduncle had visual impairment of unknown cause. Her BCVA was 0.7 in the right and 0.8 in the left. She exhibited bilateral temporal pallor of optic disc. OCT revealed microcystic macular edema in both eyes. With WES, a novel nonsense heterozygous rare variant (NM_015560: exon23: c.2350G>T: p.E784X) was located in the OPA1 gene. Case2 was a 51-year-old male. He felt bilateral visual impairment around the age of twenty and then gradually worsen. He had no family history of eye disease. His BCVA was 0.09 in the right and 0.1 in the left. He exhibited bilateral temporal pallor of optic disc. Microsystic macular edema wasn’t detected by OCT in both eyes. A novel missense heterozygous rare variant (NM_015560: exon2: c.320C>T: p.S107L) was located in the OPA1 gene.
With WES, we detected two novel potentially disease causing variations in OPA1 gene. Our result suggested that exome analysis was powerful tool for genetic diagnosis of hereditary optic atrophy. Accumulation of the pathogenicity findings of variants is important to improve the diagnostic rate.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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