OTOF

About OTOF

OTOF on chromosome 2p23.3 encodes otoferlin, a calcium sensing protein at the ribbon synapses of the inner hair cells of the cochlea, where it is essential for releasing neurotransmitter onto auditory nerve fibers. Variants on both copies of OTOF cause a form of autosomal recessive congenital deafness, DFNB9, which typically presents as auditory neuropathy: otoacoustic emissions are present, showing outer hair cells work, while the auditory brainstem response is absent. Some temperature sensitive variants cause hearing that worsens with fever. Because the hair cells themselves survive in early life, OTOF deafness has become a leading target for inner ear gene therapy. Because the coding sequence is too large for a single AAV vector, dual vector approaches are used, and early clinical trials reported from 2023 onward described restoration of hearing in some children. Cochlear implants are an established option.