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Genetic variants in the <jats:italic>WFS1<\/jats:italic> gene can cause Wolfram syndrome (WS) or autosomal dominant nonsyndromic low\u2010frequency hearing loss (HL). This study is aimed at investigating the molecular basis of HL in an affected Chinese family and the genotype\u2010phenotype correlation of <jats:italic>WFS1<\/jats:italic> variants. <jats:italic>Methods<\/jats:italic>. The clinical phenotype of the five\u2010generation Chinese family was characterized using audiological examinations and pedigree analysis. Target exome sequencing of 129 known deafness genes and bioinformatics analysis were performed among six patients and four normal subjects to screen suspected pathogenic variants. We built a complete WFS1 protein model to assess the potential effects of the variant on protein structure. <jats:italic>Results<\/jats:italic>. A novel heterozygous pathogenic variant NM_006005.3 c.2020G&gt;T (p.Gly674Trp) was identified in the <jats:italic>WFS1<\/jats:italic> gene, located in the C\u2010terminal domain of the wolframin protein. We further showed that HL\u2010related <jats:italic>WFS1<\/jats:italic> missense variants were mainly concentrated in the endoplasmic reticulum (ER) domain. In contrast, WS\u2010related missense variants are randomly distributed throughout the protein. <jats:italic>Conclusions<\/jats:italic>. In this family, we identified a novel variant p.Gly674Trp of <jats:italic>WFS1<\/jats:italic> as the primary pathogenic variant causing the low\u2010frequency sensorineural HL, enriching the mutational spectrum of the <jats:italic>WFS1<\/jats:italic> gene.<\/jats:p>","DOI":"10.1155\/2021\/6624744","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T02:20:09Z","timestamp":1614910809000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Missense Variant of Endoplasmic Reticulum Region of <i>WFS1<\/i> Gene Causes Autosomal Dominant Hearing Loss without Syndromic 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