Deafness: discovery of a new genetic mutation involved in hearing loss

A mouse study highlights a new risk factor for hearing loss. In question, the mutation of a thyroid hormone receptor would disrupt the hair cells, which allow us in particular to perceive high frequencies.

At the level ofinner ear, the cochlea is the organ that integrates sound. Triiodothyronine (T3), which represents the active form of a thyroid hormone, plays an essential role in the development of the cochlea and hearing. As always in biology, receptors mediate many pathways. Here, the actions of T3 can succeed thanks to the TRβ and TRα receptors, but certain mutations of Genoa coding for these receptors are likely to alter the establishment of auditory functions.

Mutations that affect TRβ are already known to lead to a resistance to thyroid hormone and are associated with deafness in humans and mice. However, much of the role of TRα in auditory function was unknown. To test whether the TRα receptor also affects this function, French researchers introduced the human mutation of the THRA gene encoding TRα into mice.

THRA Mutation Leads to Damaged Outer Hair Cells

” It turns out that the implantation of certain cells of theinner ear animal then becomes abnormal “, Explain in a press release from Inserm Jing Wang of the Montpellier Neuroscience Institute, co-author of the study. ” It is hair cells external, normally responsible for amplifying the vibes sound and which contribute to the distinction of their different frequencies. This anomaly leads to a loss of perception of high frequencies by mice carrying the mutation. »

In more detail, the outer hair cells of the cochlea of ​​these mice were abnormally oriented (about 20%) or absent, and appear more vulnerable to different types of stress: exposure to loud sounds, drugs harmful to hearing (called “ototoxic”) or even oxidative mechanisms linked to aging. Additionally, the researchers report that there are fewer constituent nerve fibers of the auditory nerve in the presence of the THRA gene mutation.

Thus, the TRα receptor is necessary for the proper development and maintenance of the function of the outer hair cells. This suggests that patients with mutations in the THRA gene may be at increased risk for hearing loss with time. In France, a few people have just been identified as carriers of this mutation.

Conduct human trials

” In order to find out if these alterations are found in humans, we will receive patients who have been identified with this mutation and conduct tests that will specifically focus on the functionality of their outer hair cells.says Jing Wang. If the hearing assessment of these people reveals an impairment comparable to that observed in our model murinewe will make them aware of the risk incurred, while waiting to validate all of our data. »

In addition to a regular evaluation of their hearing, it will then be recommended to these patients to avoid taking ototoxic drugs, as well as exposure to sound levels excessive. In the longer term, increasing the number of functional hair cells could be an interesting therapeutic approach.