Novel biallelic variants in the PLEC gene are associated with severe hearing loss

Pediatric auditory neuropathy spectrum disorder is a particular type of hearing loss caused by abnor-mal sound transmission from the cochlea to the brain. It is due to defective peripheral synaptic function or improper neuronal conduction. Using trio whole-exome sequencing, we have identified novel bial-lelic variants in the PLEC gene in three individuals with profound deafness from two unrelated families. Among them, one pediatric patient diagnosed with auditory neuropathy spectrum disorder had a good cochlear implantation outcome. The other two adult patients were diagnosed with non-syndromic hear-ing loss. Studies in mice and zebrafish confirmed that plectin is developmentally expressed in the inner ear. Moreover, plectin's knockdown resulted in a reduction of synaptic mitochondrial potential and loss of ribbon synapses, reinforcing the idea of a role for plectin in neuronal transmission. Altogether, the results presented here, point to a new unconventional role for plectin in the inner ear. Contrary to the well-characterized association of plectin to skin and muscle diseases, we found that specific plectin mu-tations can result in hearing loss with no other clinical manifestations. This is important because 1) it provides evidence of plectin's involvement in inner ear function and 2) it will help clinicians at the time of diagnosis and treatment.& COPY; 2023 Elsevier B.V. All rights reserved.

Automated summary

Pediatric auditory neuropathy spectrum disorder is a type of hearing loss caused by abnormal sound transmission, and a study has identified novel biallelic variants in the PLEC gene in three individuals with profound deafness, highlighting the involvement of plectin in inner ear function. The study also showed that plectin knockdown resulted in a reduction of synaptic mitochondrial potential and loss of ribbon synapses, suggesting its role in neuronal transmission. This finding is important for diagnosis and treatment of hearing loss.