Dominant optic atrophy in a Japanese family with OPA1 frameshift mutation (V942fsX966)

The authors report the ophthalmic characteristics of a male proband in a Japanese family with autosomal dominant optic atrophy (DOA) harboring a frameshift mutation in the OPA1 gene.

Conventional ophthalmologic examinations including static automated perimetry were performed, as well as assessment of the three-generation family history. The peripapillary retinal nerve fiber layer (RNFL) was evaluated using scanning laser polarimetry. Mutation screening of the OPA1 gene was performed with polymerase chain reaction amplification and direct sequencing.

A frameshift mutation (p.V942fsX966) was identified in the proband and his mother. In comparison with the adolescent onset of visual loss in the proband and his maternal grandfather, the mother presented with only subtle temporal disc pallor and has never been aware of any visual disturbances. Symmetric thinned peripapillary RNFL was detected in the proband, whose visual field abnormalities were limited to central scotomas and were without mean deviation worsening between 11 to 17 years of age in both eyes. The proband's logMAR visual acuity (0.52 to 0.7) has remained almost unchanged for more than 10 years since initial evaluation at age 10.

The OPA1 mutation may be correlated with slow progression of DOA, and with phenotypic variations within the family. Further study is necessary to determine whether symmetric thinned peripapillary RNFL represents a feature of DOA.