Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect

摘要: Purpose Autosomal dominant optic atrophy (ADOA, OMIM 165500), an inherited neuropathy that leads to retinal ganglion cell degeneration and reduced visual acuity during the early decades of life, is mainly associated with mutations in OPA1 gene. Here we report a novel ADOA phenotype new pathogenic gene mutation. Methods The patient, 62-year-old woman, was referred for acute, painless, severe loss her right eye. Acute left eye occurred year after initial presentation. MRI confirmed diagnosis isolated atrophic bilateral neuropathy. We performed DNA sequencing entire coding sequence exon/intron junctions gene, searched mitochondrial responsible Leber hereditary by entirely DNA. Mitochondrial respiratory chain complex activity morphology were investigated skin fibroblasts from patient controls. Results identified heterozygous missense mutation (c.2794C>T) exon 27 resulting amino acid change (p.R932C) protein. This mutation, which affects highly conserved acids, has not been previously reported, absent 400 control chromosomes. analysis did reveal any or mutations. investigation revealed coupling defect oxidative phosphorylation larger proportion short mitochondria than Conclusions presence indicates this sporadic, late-onset acute case related energetic defect. suggests mutational screening would be justified atypical cases nerve no evident cause.