Whole exome sequencing of six Chinese families with hereditary non-syndromic hearing loss

Abstract

Objectives: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with about 152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.

Methods: After excluding the pathogenic/likely pathogenic variants in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.

Results: Biallelic variants were identified in all deaf patients. Among these six families, 10 potentially causative variants, including 3 reported and 7 novel variants, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. These novel variants are thought to be pathogenic or likely pathogenic for theirs predicted damage function upon the protein as while as cosegregated with the deafness phenotype. The variants in MYO15A were frequent with 7/10 candidate ones.

Conclusion: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the pathogenic/likely pathogenic variants spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

Keywords: Deafness; Genetic etiology; Non-syndromic; Variant; Whole-exome sequencing.