# The Segregation of p.Arg68Ter-CLDN14 Mutation in a Syrian Deaf Family, Phenotypic Variations, and Comparative Analysis with the GJB2 Gene

## TL;DR

This study identifies a genetic mutation in a Syrian family with hearing loss and compares it to another gene involved in deafness.

## Contribution

The study identifies a novel nonsense mutation in the CLDN14 gene and compares it with GJB2 to explain phenotypic differences.

## Key findings

- A nonsense mutation in the CLDN14 gene was found to segregate with hearing loss in a Syrian family.
- The CLDN14 mutation was not present in the control population, supporting its pathogenicity.
- A comparative analysis between CLDN14 and GJB2 was conducted to explain differences in mutation frequency.

## Abstract

Hearing impairment, a rare inherited condition, is notably prevalent in populations with high rates of consanguinity. The most common form observed globally is autosomal recessive non-syndromic hearing loss. Despite its prevalence, this genetic disorder is characterized by a substantial genetic diversity, making diagnosis and screening challenging. The emergence of advanced next-generation sequencing (NGS) technologies has significantly advanced the discovery of genes and variants linked to various conditions, such as hearing loss. In this study, our objective was to identify the specific variant causing hearing loss in a family from Syria using clinical exome sequencing. The proband in the family exhibited profound deafness as shown by pure-tone audiometry results. The analysis of the different variants obtained by NGS revealed the presence of a nonsense mutation within the CLDN14 gene. Through Sanger sequencing, we verified that this variant segregates with the disease and was not present in the control population. Moreover, we conducted a comprehensive review of all reported deafness-related CLDN14 mutations and their associated phenotypes. Furthermore, we endeavored to carry out a comparative analysis between the CLDN14 and GJB2 genes, with the objective of identifying potential factors that could explain the notable discrepancy in mutation frequency between these two genes.