Unraveling the Diversity of <i>GJB2</i> Mutations in Nonsyndromic Hearing Loss: A Comprehensive Study in the Moroccan Population

Abstract

<b><i>Introduction:</i></b> Despite the high genetic heterogeneity of hearing loss, mutations in the <i>GJB2</i> gene are a major cause of autosomal recessive nonsyndromic hearing loss (NSHL) worldwide. However, the mutation profile of <i>GJB2</i> in NSHL is under-investigated in Morocco, especially among simplex cases. This study aimed to identify the spectrum and frequency of <i>GJB2</i> mutations in the Moroccan population among simplex and multiplex families with NSHL. <b><i>Methods:</i></b> Moroccan families with NSHL were selected according to well-defined criteria. Selected families were screened for <i>GJB2</i> gene variants using direct sequencing of the entire coding region of <i>GJB2</i>. <b><i>Results:</i></b> A total of 145 affected individuals from 115 families with NSHL were included in this study (49 simplex, 66 multiplex). Mutations in the <i>GJB2</i> gene were noted in 28.69% of the families (33/115), of which 75.75% were multiplex families and 24.24% were simplex. In total, seven different mutations were detected: c.35delG(p.G12fs), c.551G&gt;A(p.R184Q), c.139G&gt;T(p.E47X), c.109G&gt;A(p.V37I), c.167delT(p.L56fs), c.617A&gt;G(p.N206S), c.94C&gt;T(p.R32C). The last three mutations have not previously been reported in Morocco. The most common <i>GJB2</i> mutation was c.35delG (21.73%), followed by p.V37I (2.60%) and p.E47X (1.73%). <b><i>Conclusions:</i></b> Our study confirms a high prevalence of <i>GJB2</i> variants in the Moroccan population, particularly the c.35delG mutation. Additionally, we have identified previously unreported or rarely reported mutations, revealing a greater diversity of <i>GJB2</i> mutations. These findings emphasize the importance of comprehensive screening beyond the 35delG mutation for patients with NSHL, regardless of their family history. Integrating this approach into clinical care will enhance diagnosis and management of hearing loss in the Moroccan population.