The dysfunction of OPA1, a dynamin GTPase involved in mitochondrial fusion, is responsible for a large spectrum of neurological disorders, each of which includes optic neuropathy.
This study expanded the OPA1 mutation spectrum, and our results showed that OPA1 mutation is another common cause of childhood-onset hereditary optic neuropathy in Chinese pediatric patients, especially those with disease onset during preschool age.
The association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the association of defective mitochondrial dynamics, mtDNA multiple deletions, and altered mitophagy with parkinsonism.
In summary, we provide genetic and functional evidence that deep intronic mutations in OPA1 can cause optic atrophy and explain disease in a substantial share of families with unsolved inherited optic neuropathies.
This study describes a clinical series of 40 patients from Saudi Arabia with a positive DOA phenotype (i.e., decreased visual acuity during the first 2 decades of life, temporal or global optic disc pallor, and absence of other neurological or ophthalmological diseases that could explain the optic neuropathy) who underwent molecular genetic testing for OPA1 (and, in some cases, for OPA3).
These results suggest that the clinical spectrum of the OPA1-associated optic neuropathies may be larger than previously described, and that spontaneous recovery may occur in cases harboring an exon 5b mutation.