Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy

Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy occurring in 1 in 50,000 individuals 1 , 2 , 3 that features progressive loss in visual acuity leading, in many cases, to legal blindness 4 , 5 , 6 , 7 , 8 . Phenotypic variations 5 and loss of retinal ganglion cells 9 , 10 , as found in Leber hereditary optic neuropathy (LHON), have suggested possible mitochondrial impairment 11 , 12 . The OPA1 gene has been localized to 3q28–q29 (refs 13 – 19 ). We describe here a nuclear gene, OPA1 , that maps within the candidate region and encodes a dynamin-related protein localized to mitochondria. We found four different OPA1 mutations, including frameshift and missense mutations, to segregate with the disease, demonstrating a role for mitochondria in retinal ganglion cell pathophysiology.