Compound heterozygous GJB2 mutations associated to a consanguineous Han family with autosomal recessive non-syndromic hearing loss

Abstract

Conclusion: This study demonstrates that the gap junction protein beta-2 gene (GJB2) p.R32C and p.L79Cfs*3 variants are associated to a consanguineous family with autosomal recessive non-syndromic hearing loss (ARNSHL). The p.R32C variant is found for the first time in the NSHL patients of Han Chinese origin. The finding sheds new light on the accurate genetic diagnosis and counseling for the family. Objective: ARNSHL is a highly heterogeneous genetic disease. ARNSHL usually displays non-progressive congenital or pre-lingual deafness. In this study, the aim is to detect the disease-causing mutation(s) in a Han family with ARNSHL. Methods: A consanguineous Han family with ARNSHL was enrolled. Two hundred ethnicity-matched unrelated subjects without any hearing impairments were used as normal controls. Exome sequencing and Sanger sequencing were applied to identify the causative mutation in the ARNSHL family. Results: Compound heterozygous variants c.94C > T (p.R32C) and c.235delC (p.L79Cfs*3) in the GJB2 gene were identified in the two patients of the ARNSHL family, and the heterozygous GJB2 c.94C > T and c.235delC variants were identified in his unaffected father and mother, respectively. The two variants in the GJB2 gene were absent in the 200 unrelated controls.

Keywords:

• Exome sequencing
• deafness
• GJB2 gene
• mutation

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding information

This work was supported by grants from the National Natural Science Foundation of China (grant number 81271921 and 81441033), the Foster Key Subject of the Third Xiangya Hospital Clinical Laboratory Diagnostics (H.D.), Zhishan Lead Project of the Third Xiangya Hospital (H.D.), Hunan Provincial Innovation Foundation for Postgraduate, China (CX2014B109), and the Top-notch Innovative Doctoral Scholarship of Central South University, China (2014bjjxj039).