A novel OPA1 mutation in a patient with severe, acute and late‐onset Autosomal Dominant Optic Atrophy

Abstract

Abstract Purpose We report the first case of acute and late‐onset Autosomal Dominant Optic Atrophy with a novel mutation. Autosomal Dominant Optic Atrophy (ADOA) is an inherited primary optic neuropathy that leads to reduced visual acuity. ADOA has often been associated with mutations in OPA1 gene. OPA1 encodes a large dynamin‐related GTPase, involved in mitochondrial structure, mitochondrial DNA maintenance and apoptosis regulation. Methods We conducted direct DNA sequencing of the entire coding sequence and the exon/intron junctions of OPA1 gene. Results A 62‐year‐old woman noticed blurred vision with a central scotoma. Visual loss was sudden, painless and severe in her right eye. Papillary edema was noted. Left visual loss occurred one year after initial presentation. The ophthalmoscopic feature of our patient was diffuse optic disc atrophy. MRI examination confirmed the diagnosis of isolated bilateral optic neuropathy. We did not found any neurological, metabolic, toxic, or ophtalmic causes. One novel heterozygous missense mutation in exon 27 was characterized. This mutation has not been previously reported, was absent in 400 control chromosomes and affected highly conserved amino acids. Conclusion The age of onset, like ADOA penetrance must be accepted to be more variable than initially thought, including late‐onset cases. The presence of an OPA1 mutation reveales that this sporadic late‐onset and acute case of optic neuropathy is related to ADOA. This result shows that the mutation screening of OPA1 gene could be justified in every case of optic nerve atrophy with no clear cause.