Abstract
Autosomal Dominant Optic Atrophy (ADOA) is characterized by the selective degeneration of retinal ganglion cells. The occurrence of mutations in the gene encoding the dynamin-like GTPase protein Optic Atrophy 1 (OPA1) has been observed in about 60-70% of ADOA cases. A subset of missense mutations, mostly within the GTPase domain, has recently been associated with a syndromic ADOA form called "OPA1 plus" phenotype presenting, at muscle level, mitochondrial DNA (mtDNA) instability. In this study we disclosed two OPA1 gene mutations in independent probands from two families affected by OPA1 plus phenotype: the previously reported c.985-2A>G substitution and a novel microdeletion (c.2819-1_2821del). The correlation between genotype and phenotype and the effects of these variants at the transcript level and in the muscle tissue were investigated, confirming the broad complexity in the phenotypic spectrum associated with these OPA1 mutations.