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

Abstract

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.

Neurosensory Affectation in Patients Affected by Wolfram Syndrome: Descriptive and Longitudinal Analysis

“…In our case, the most severe cases occurred in exon 4 of the WFS1 gene. This partially agrees with Zhao et al [ 28 ], since these authors also detected that the mutation in exon 4 shows a profound or severe affectation phenotype. In contrast, it has been detected that mutation in exon 4 may not alter hearing loss [ 29 ].…”

“…In contrast, it has been detected that mutation in exon 4 may not alter hearing loss [ 29 ]. However, most mutations occur in exon 8 [ 28 , 30 ], which, again, shows the complexity of the WS.…”

Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review

“…The WFS1 gene encodes “Wolframin”, a transmembrane protein located in the endoplasmic reticulum and ubiquitously expressed [ 191 ]. DFNA6/14/38 was largely described in the United States of America [ 192 , 193 , 194 , 195 , 196 , 197 ], Japan [ 198 , 199 , 200 , 201 , 202 , 203 ], and China [ 133 , 182 , 204 , 205 , 206 , 207 , 208 , 209 , 210 ]. In Europe, DFNA6/14/38 was reported in Dutch [ 191 , 211 , 212 , 213 ], Swiss [ 214 ], Danish [ 215 ], Hungarian [ 216 ], Finnish [ 217 ], and German [ 218 ] families.…”

In-silico analysis of nsSNPs in human CYP3A4/5 and their effects on drug-enzymes interactions of FDA-approved COVID-19 antiviral drugs: A pharmacogenetic study

“…Currently, in silico technologies can determine the harmfulness of single nucleotide polymorphisms (SNPs) via computer procedures 11 . Predicting the mutations' effects is more accurate when combining multiple algorithms rather than using one software 12 . In a simulated environment, advanced approaches like molecular docking and molecular dynamics simulations can accurately examine protein features including chemical properties, structure, and molecule interactions 13 .…”