• dominant optic atrophy plus syndrome

This report describes optic atrophy plus syndrome, now designated by OMIM as 'optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy'; it is also called dominant optic atrophy plus syndrome (DOA+) or syndromic optic atrophy. Optic atrophy plus syndrome exhibits autosomal dominant inheritance. The human gene implicated in this disease is OPA1, which encodes a protein that localizes to the inner mitochondrial membrane and regulates several important cellular processes including stability of the mitochondrial network and mitochondrial bioenergetic output. There is a single orthologous gene in Drosophila, Dmel\Opa1. The human OPA1 gene is implicated in multiple other diseases; see MIM:605290. For information on fly models of disease using the fly gene, see 'optic atrophy syndromes, OPA1-related' (FBhh0000642).

Multiple UAS constructs of the human Hsap\OPA1 gene, including wild-type and variants implicated in disease, have been introduced into flies. See the 'Disease-Implicated Variants' table below. Partial heterologous rescue (functional complementation) has been demonstrated. Variants of Hsap\OPA1 implicated in disease fail to rescue or exhibit a lower degree of rescue. More severe mutations are associated with optic atrophy plus syndrome (subject of this report) and less severe with this disease, optic atrophy 1 (FBhh0000644). This analysis allows quantitative evaluation of loss-of-function severity by comparing the rescue capabilities of known or newly identified variants, thus allowing rapid determination of the disease subtype.

[updated Oct. 2024 by FlyBase; FBrf0222196]