OPA1

About OPA1

OPA1 on chromosome 3q29 encodes a dynamin related GTPase of the mitochondrial inner membrane that drives fusion of the inner membrane and maintains the folded cristae on which the respiratory chain is organized. It also helps maintain mitochondrial DNA and protects cells against apoptosis. Heterozygous pathogenic variants cause autosomal dominant optic atrophy, also known as Kjer optic atrophy after the Danish ophthalmologist Poul Kjer, the most common inherited optic neuropathy alongside Leber hereditary optic neuropathy. The disease results from loss of retinal ganglion cells, whose long unmyelinated axons within the eye are especially dependent on mitochondrial energy. It typically causes slowly progressive bilateral loss of visual acuity beginning in childhood, central or cecocentral visual field defects, color vision loss, often in the blue yellow axis, and pallor of the optic disc, particularly its temporal side. Severity varies widely, even within families, and penetrance is incomplete. Some variants, often missense changes in the GTPase domain, cause a multisystem dominant optic atrophy plus syndrome with deafness, ataxia, myopathy, peripheral neuropathy, and progressive external ophthalmoplegia, associated with mitochondrial DNA deletions. Variants on both copies cause severe early onset neurological disorders. Gene therapy and other approaches are being investigated.