This report describes optic atrophy with neurological involvement, one of several diseases associated with the human gene ATAD3A. ATAD3A encodes a mitochondrial transmembrane protein that impacts multiple activities and processes in mitochondria. This newly described form of optic atrophy is the mildest of several diseases associated with ATAD3A (see MIM:612316); it exhibits autosomal dominant inheritance. A disease model for Harel-Yoon syndrome, one of the other diseases associated with ATAD3A, has been developed in Drosophila (see FBhh0000622).
In Drosophila there is a single gene orthologous to ATAD3A, Dmel\bor. Multiple genetic reagents have been generated for bor, including loss-of-function alleles, RNAi-targeting constructs, and mutations analogous to disease-implicated variants. Dmel\bor is also orthologous to two additional genes in human, ATAD3B and ATAD3C. None of the human ATAD3 genes has been introduced into flies.
A specific variant of the ATAD3A gene, ATAD3A:p.Arg466Cys , has been found to be associated with optic atrophy with neurological involvement. The analogous mutation in Dmel\bor has been created and characterized; see the 'Disease-Implicated Variants' table below. The role of aberrant cholesterol metabolism in ATAD3A-related disease has been investigated using this model.
Autosomal optic atrophy is genetically heterogenous; all currently identified causative genes appear to be associated with mitochondrial organization or function (Strachan et al., 2021; pubmed:34867178). Drosophila has been used as a disease model for two other forms of optic atrophy: see FBhh0000642 and FBhh0001305.
[updated July 2024 by FlyBase; FBrf0222196]
A slowly progressive optic atrophy with signs of peripheral neuropathy (Munoz-Oreja et al., 2024; pubmed:38242545; FBrf0259414).
This disease, optic atrophy with neurological involvement, exhibits autosomal dominant inheritance (Munoz-Oreja et al., 2024; pubmed:38242545; FBrf0259414).
ATAD3A encodes a ubiquitously expressed mitochondrial transmembrane protein that contributes to mitochondrial dynamics, nucleoid organization, protein translation, cell growth, and cholesterol metabolism. [Gene Cards, ATAD3A; 2024.07.09]
Many to one: 3 human genes to 1 Drosophila gene.
High-scoring ortholog of human ATAD3A; moderate-scoring ortholog of ATAD3B and ATAD3C (1 Drosophila to 3 human).
