Abstract
BACKGROUND/OBJECTIVES: Hearing loss (HL) is a significant global health concern, affecting approximately 1 in every 1000 newborns, with over half of these cases attributed to genetic factors. This study focuses on identifying the genetic basis of autosomal recessive non-syndromic hearing loss (ARNSHL) in a consanguineous Emirati family. METHODS: Clinical exome sequencing (CES) was performed on affected members of the family, followed by Sanger sequencing to validate the findings. Specific primers were used for PCR amplification of target CDH23 exons. Mutations were analyzed using various computational tools to assess their pathogenicity. RESULTS: We identified two heterozygous mutations in the CDH23 gene: a novel nonsense variant (c.264G>A, p.Trp88Ter) and a missense variant (c.5168G>A, p.Arg1723His). Both mutations were found in trans configuration, suggesting a compound heterozygous state contributing to the phenotype. In silico analysis predicted a significant impact on protein function, potentially leading to the observed ARNSHL. CONCLUSIONS: This study emphasizes the complexity of genetic factors in hearing loss, particularly in highly consanguineous populations. The identification of both nonsense and missense mutations in the CDH23 gene enhances understanding of its role in hearing loss and provides essential insights for genetic counseling and future therapeutic strategies.