OPA1-related sensorineural hearing loss

Purpose The OPA1 gene, encoding a dynamin-like mitochondrial GTPase, is responsible for autosomal dominant optic atrophy (ADOA, OMIM #165500), which can be associated with extra-ocular abnormalities including sensorineural deafness.The purpose of this study is to determine, in a large series of patients carrying OPA1 mutations, the prevalence of the R445H mutation and of rarer OPA1 mutations in patients with ADOD and to describe the phenotype associated with these rarer mutations. Methods We retrospectively reviewed the files of all the OPA 1 patients with documented deafness diagnosed in our laboratory between 2003 and 2011. Results In our series, deafness occurred in 6.4% of OPA1 patients. Hearing loss occurred as the first sign of the disease in one third of the patients, prior to visual loss. In addition to the most common mutation responsible for ADOA and deafness (R445H), we report 6 additional mutations responsible for this association. Conclusion Deafness can be associated with dominant optic atrophy, due to OPA1 mutations, other than the classical R445H mutation. Unexplained sensorineuronal hearing loss can even be the first event and its association to optic atrophy and should prompt molecular genetic analysis, which can lead to an appropriate diagnosis.