Background. Nonsyndromic low-frequency sensorineural hearing loss (LFSNHL) is an uncommon form of hearing loss (HL) that typically affects frequencies at 2000 Hz and below. Heterozygous variants in the WFS1 gene at the DFNA6/14/38 locus are considered a common cause of LFSNHL. To date, 34 different pathogenic genetic variants have been reported to cause LFSNHL with seven of these variants identified in the Chinese population. However, limited reports are available on the association between WFS1 gene and LFSNHL. Here, we report a five-generation Chinese family with an autosomal dominant inheritance pattern of postlingual and progressive LFSNHL. Methods. Routine clinical and audiological examinations were performed on 16 affected and 7 healthy members in this family. The targeted next-generation sequencing of 127 known deafness genes was performed to identify variants in affected individuals. Sanger sequencing were further employed to confirm the pathogenic variant identified. Results. A novel heterozygous pathogenic genetic variant c.2530G > T (p.Ala844Ser) was identified in the WFS1 gene in all patients of this family. The mutated Ala residue is evolutionarily conserved and cosegregated with HL. The variant was predicted to be deleterious by MutationTaster, PolyPhen-2, LRT, and Fathmm software. Conservation analysis and 3D protein structure model indicated that the variant caused a structural change in the protein. Conclusions. Our present study identifies a novel heterozygous WFS1 variant associated with LFSNHL in a Chinese family.

Hearing loss is currently one of the most prevalent sensory disorders worldwide. Because both the blood–labyrinth barrier and the limited blood circulation in the inner ear restrain the effective delivery of most drugs to the inner ear tissues, current treatments for hearing loss are limited to mainly medication, hearing devices and cochlear surgery for therapeutic purposes, whereas treatments lack a noninvasive targeted drug-delivery system. With the continuously rapid development of new nanomaterials, the nanodelivery systems are expected to provide a potentially effective method of clinical treatment for hearing loss. This paper reviews the advantages and disadvantages of the commonly used drug-delivery methods and novel nanomaterials for inner ears as well as advancements in the targeted treatment of hearing loss.