Non‐OPA1 genetic causes of dominant optic atrophies

Abstract

AbstractDominant optic atrophy (DOA) is one of the most common forms of inherited optic nerve disease. The prevalence of DOA has been estimated to range from 1:16 000–1:50 000 in different populations. Clinical expression of DOA is highly variable and reduced penetrance is rather common which may hamper to establish the proper mode of inheritance. Dominant optic atrophy is a genetically heterogeneous condition with mutations in the OPA1 gene being by far the most common cause of DOA. Yet the knowledge about other genetic causes of DOA is still limited and sometimes equivocally. In recent years it became apparent that ‐ in term of its genetic basis ‐ DOA is just part of a continuous spectrum of syndromic neurodegenerative disease in many of which optic atrophy is only one clinical feature. Notably, the vast majority of the involved genes encode for proteins which are imported into mitochondria and exert diverse biological functions therein. In this presentation, I will give an overview on the current knowledge of non‐OPA1 genetic causes of dominant optic atrophies and the potential molecular mechanisms underlying the clinical outcome as DOA or syndromic neurodegenerative disease.