Analysis of SLC26A4 Gene in Individuals with Non Syndromic Hearing Impairment in  Relation with GJB2 Associated Mutations

Krishna  Rajalakshmi; Jayakumar  Thirunavukkarasu; Meenu Ambika  Vikraman; Santosh  Maruthy; Charles  Sylvester; Rajesh  Kundapur

doi:10.18502/ajmb.v15i2.12023

Krishna Rajalakshmi Department of Audiology, All India Institute of Speech and Hearing, Naimisham Campus, Manasagangothri, Mysore, India 570006
Jayakumar Thirunavukkarasu Department of Speech-Language Sciences, All India Institute of Speech and Hearing, Naimisham Campus, Manasagangothri, Mysore, India 570006
Meenu Ambika Vikraman Department of Audiology, All India Institute of Speech and Hearing, Naimisham Campus, Manasagangothri, Mysore, India 570006
Santosh Maruthy Department of Speech-Language Sciences, All India Institute of Speech and Hearing, Naimisham Campus, Manasagangothri, Mysore, India 570006
Charles Sylvester Unit for Human Genetics, All India Institute of Speech and Hearing, Naimisham Campus, Manasagangothri, Mysore, India 570006
Rajesh Kundapur Unit for Human Genetics, All India Institute of Speech and Hearing, Naimisham Campus, Manasagangothri, Mysore, India 570006

DOI: https://doi.org/10.18502/ajmb.v15i2.12023

Keywords: Child, Genotype, Hearing loss, High-throughput nucleotide sequencing, Humans, Mutation

Abstract

Background: Hearing Loss (HL) is the most common sensory disorder. HL commonly ranges from mild to severe. Persons with HL face difficulty in hearing conversations or sounds through one ear or both ears, which impacts one’s ability to interact with others. Hence it is a communicable disorder that makes people socially isolated, lonely, and frustrated. HL in children severely affects language development. The people who are referred to as 'Deaf' with very little or no hearing capabilities, are considered as having profound hearing loss. More than 124 genes are causative for Non-Syndromic HL (NSHL) with varying inheritance, among which the SLC26A4 mutations are the second commonest cause of hereditary HL across the globe.

Methods: Samples from 70 NSHL patients were analyzed through Next-Generation Sequencing (NGS) and generated five pathogenic variants [N246fs (rs918684449), K564fs (rs746427774), F122fs, V239D (rs111033256), T721M (rs121908363)] each with frequency of 1.42%. Three missense variants [S399P (rs747431002), L597S (rs55638457), and G6V (rs111033423)] were reported under the "uncertain" category. All the collected samples were further genotyped to look for the possibility of having GJB2 and HL-associated mutations.

Results: Out of five SLC26A4 pathogenic mutations N246fs (rs918684449) and K564fs (rs746427774) were observed in samples which were positive for GJB2-HL associated candidate mutations [W24X (rs104894396), Q124X (rs397516874) and W77X (rs80338944)]. Similarly, pathogenic variants F122fs, V239D (rs111033256) and T721M (rs121908363) were observed in patient samples which were negative for GJB2-HL associated mutations.

Conclusion: Our data will expand the list of variants underlying NSHL and encourage further genotype SLC26A4 gene concerning the south Indian population with a large sample size.