Mutation analysis of the WFS1 gene in a Chinese family with autosomal-dominant non-syndrome deafness

To analyse the pathogenic genes and mutations of a family with hereditary deafness. We recruited a three-generation family with NSHL. A detailed medical history inquiry and related examinations were performed. Next-generation sequencing (NGS) was used to confirm the gene mutation in the proband, and Sanger sequencing was used for verification. The effect of the WFS1 mutation on the function and structure of the wolframin protein was predicted by multiple computational software. From the Gene Expression Omnibus (GEO) database, we obtained GSE40585 dataset and performed enrichment analyses. The family clinically manifested as autosomal dominant NSHL. A novel WFS1 c.2421C>G (p.Ser807Arg) mutation was identified in four affected individuals in the pedigree . The p.Ser807Arg mutation is a highly conserved residue and causes an increase in protein stability. It had an important influence on not only amino acid size, charge and hydrophobicity but also protein intermolecular hydrogen bonding and spatial structure. There were differentially expressed genes (DEGs) in GSE40585 dataset. Enrichment analysis revealed that DEGs mainly functioned in amino acid metabolism, signal transduction and dephosphorylation. We reported a novel mutation c.2421C>G (p.Ser807Arg in WFS1. This study expands the mutation spectrum of WFS1.