Disease relevance of OPA3

• Milder mutations in OPA3 should be sought in patients with optic atrophy with later onset, even in the absence of additional neurological abnormalities [1].
• Other hereditary retinopathies and optic neuropathies were unlikely because of inclusion and exclusion criteria, because ERGs were normal, and because no patient had pathogenic sequence changes in the OPA1 or OPA3 genes [2].
• OPA3 gene mutations responsible for autosomal dominant optic atrophy and cataract [3].
• We have screened 13 patients with neurological abnormalities and 3-methylglutaconic aciduria (3MGA) for mutations in the OPA3 gene, which are known to be the cause of Costeff syndrome (optic atrophy, chorea and spasticity; type III 3MGA) [4].
• OPA3 mutations (IVS1-1G>C) were identified in 2 patients with the classic phenotype of type III 3MGA, but not in the other 11 patients with differing non-Costeff phenotypes associated with developmental delay and neurological signs and symptoms as described [4].

High impact information on OPA3

• The FLJ22187-cDNA clone, which we identified as the OPA3 gene, consists of two exons and encodes a peptide of 179 amino acid residues [1].
• To isolate the causative gene, OPA3, we sequenced four genes within the critical interval and identified, in the intronic sequence of a gene corresponding to cDNA clone FLJ22187, a point mutation that segregated with the type III MGA phenotype [1].
• 3-Methylglutaconic aciduria type I, Barth syndrome, and Costeff syndrome were excluded as the activity of 3-methylglutaconyl-CoA hydratase, the cardiolipin levels, and molecular analysis of the OPA3 gene, respectively, showed no abnormalities [5].
• We performed biochemical and genetic investigations, including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydratase activity, cardiolipin levels, OPA3 gene analysis and measurement of the oxidative phosphorylation in four female patients with 3-methylglutaconic aciduria [5].
• The presence of the disorder in an Iraqi-Jewish genetic isolate led to mapping of the OPA3 gene to chromosome 19q13.2-q13.3, followed by isolation of the gene itself [6].

Biological context of OPA3

• OPA3 consists of two exons and codes for a peptide of 179 amino acids [6].

Anatomical context of OPA3

• Iraqi-Jewish patients with type III MGA are homozygous for a splice site founder mutation in OPA3 (IVS1-1G>C) which abolishes mRNA expression in fibroblasts [6].

References