AUTHOR=Ali Amanat , Tabouni Mohammed , Kizhakkedath Praseetha , Baydoun Ibrahim , Allam Mushal , John Anne , Busafared Faiza , Alnuaimi Ayesha , Al-Jasmi Fatma , Alblooshi Hiba 

TITLE=Spectrum of genetic variants in bilateral sensorineural hearing loss

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1314535

DOI=10.3389/fgene.2024.1314535

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Hearing loss (HL) is an impairment of auditory function with identified genetic forms that can be syndromic (30%) or non-syndromic (70%). HL is genetically heterogeneous, with more than 1,000 variants across 150 causative genes identified to date. The genetic diagnostic rate varies significantly depending on the population being tested. Countries with a considerably high rate of consanguinity provide a unique resource for studying rare forms of recessive HL. In this study, we identified genetic variants associated with bilateral sensorineural HL (SNHL) using whole-exome sequencing (WES) in 11 families residing in the United Arab Emirates (UAE).</p><p><bold>Results</bold>: We established the molecular diagnosis in six probands, with six different pathogenic or likely pathogenic variants in the genes <italic>MYO15A</italic>, <italic>SLC26A4</italic>, and <italic>GJB2</italic>. One novel nonsense variant, <italic>MYO15A</italic>:<italic>p</italic>.Tyr1962Ter*, was identified in a homozygous state in one family, which has not been reported in any public database. <italic>SLC26A4</italic> and <italic>GJB2</italic> were found to be the most frequently associated genes in this study. In addition, six variants of uncertain significance (VUS) were detected in five probands in the genes <italic>CDH23</italic>, <italic>COL11A1</italic>, <italic>ADGRV1</italic>, <italic>NLRP3</italic>, and <italic>GDF6</italic>. In total, 12 variants were observed in eight genes. Among these variants, eight missense variants (66.7%), three nonsense variants (25.0%), and one frameshift (8.3%) were identified. The overall diagnostic rate of this study was 54.5%. Approximately 45.5% of the patients in this study came from consanguineous families.</p><p><bold>Conclusion:</bold> Understanding the genetic basis of HL provides insight for the clinical diagnosis of hearing impairment cases through the utilization of next-generation sequencing (NGS). Our findings contribute to the knowledge of the heterogeneous genetic profile of HL, especially in a population with a high rate of consanguineous marriage in the Arab population.</p>