A novel heterozygous SIX1 missense mutation resulted in non-syndromic unilateral hearing loss

Ang Li; Siwen Liu; Peng Zhang; Xintong Hu; Guiying Li; Weiyue Gu; Yanfang Jiang

doi:10.3389/fgene.2022.1047230

A novel heterozygous SIX1 missense mutation resulted in non-syndromic unilateral hearing loss

Front Genet. 2022 Nov 22:13:1047230. doi: 10.3389/fgene.2022.1047230. eCollection 2022.

Authors

Ang Li¹, Siwen Liu¹, Peng Zhang¹, Xintong Hu¹, Guiying Li², Weiyue Gu², Yanfang Jiang¹

Affiliations

¹ Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China.
² Chigene (Beijing) Translational Medical Research Center Co., Ltd, Beijing, China.

Abstract

Familial non-syndromic unilateral hearing loss (NS-UHL) is rare and its genetic etiology has not been clearly elucidated. This study aimed to identify the genetic cause of NS-UHL in a three-generation Chinese family. Detailed medical history consultation and clinical examination were conducted. Further, whole-exome sequencing (WES) was performed to identify the genetic etiology of the proband, and the variant was verified by Sanger sequencing. A novel missense mutation, c.533G>C (p.Arg178Thr), in the SIX homeobox 1 gene (SIX1) was identified in four patients and co-segregated with NS-UHL in a three-generation Chinese family as a dominant trait. Using bioinformatics analyses, we show that this novel mutation is pathogenic and affects the structure of SIX1 protein. These data suggest that mutations in SIX1 gene are associated with NS-UHL. Our study added the NS-UHL phenotype associated with SIX1, and thereby improving the genetic counseling provided to individuals with SIX1 mutations.

Keywords: SIX1 gene; genetic counseling; non-syndromic unilateral hearing loss; novel mutation; whole exome sequencing.