TNN is first linked to auditory neuropathy

Autosomal recessive nonsyndromic auditory neuropathy is attributed to a genetic etiology. We identified a compound heterozygous missense variant, c.G736A (p.G246S) and c.C2954T (p.T985 M) in TNN of affected patients in a pedigree via candidate gene screening and exome sequencing. To determine the genetic etiology of deafness in the pedigree with a heterozygous missense variant in the gene TNN encoding tenascin-W associated with autosomal recessive nonsyndromic auditory neuropathy, the cochlear expression of tenascin-W was evaluated at mRNA and protein levels in mice, and Tnn knock out mice were generated and utilized to study the function of Tnn in the auditory system. Immunofluores-cence stainings showed that tenascin-W was mainly expressed in the somatic cytoplasm of spiral gan-glion neurons of mice. Homozygous Tnn knockout was lethal in mice, whereas Tnn heterozygous mice showed decreases in spiral ganglion neuron density and progressive hearing loss. We demonstrate that tenascin-W is expressed in the murine cochleae and is essential for the development of spiral ganglion neurons. An abnormal expression of tenascin-W can influence the development and function of SGNs and affect the function of the auditory system.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Autosomal recessive nonsyndromic auditory neuropathy is caused by a genetic etiology. Through candidate gene screening and exome sequencing, we identified a compound heterozygous missense variant in the TNN gene of affected patients in a pedigree. Our findings demonstrate that tenascin-W plays an essential role in the development and function of spiral ganglion neurons in the murine auditory system, and abnormal expression of tenascin-W can affect the function of the auditory system.