Mutations in the otoferlin (OTOF) gene lead to profound hearing loss in humans. Interestingly, a number of missense otoferlin mutations cause hearing defects but only at higher body temperature, and the reasons for this have been elusive until now. A study published in this issue of The EMBO Journal (Strenzke et al, 2016) adds insight into the underlying mechanisms for this heat‐dependent hearing loss.
See also: N Strenzke et al (December 2016) and
C Vogl et al (December 2016)
Imagine lying in bed with a fever, tossing, and turning, trying to find a comfortable position for your aching body. To make matters worse, you are having more trouble hearing than usual and you fear the effect will be lasting. Thankfully, when the fever finally subsides, you find that your hearing returns, so that the relief you yearned for from the aches and pains is even more gratifying.
Hearing is essential for our ability to perceive the outside world, to be warned of danger, and to communicate with fellow humans. Hearing loss is therefore a crucial impairment and even more difficult to cope with if the loss occurs after the acquisition of hearing and language. It means having to adapt to an entirely new situation and, in many ways, a new life. Such is the case for patients with specific mutations of the OTOF gene. These individuals have normal hearing threshold that allows them to hear sounds well enough to avoid dangerous situations, but suffer from compromised speech recognition. They can hear a voice, but often are not able to make out what the person is saying. Moreover, for a subset of these patients, their hearing problems worsen upon exposure to heat, such as a fever.
Otoferlin is a member of the FER‐1 family of transmembrane proteins distinguished by C2 domains that are …