Mutational spectrum of SLC26A4 and SLC26A5 associated with hereditary hearing loss in Moroccan families

BACKGROUND: The solute carrier family 26 (SLC26) encodes multifunctional anion transporters that mediate the transmembrane exchange of monovalent and divalent anions. While pathogenic variants in several SLC26 genes cause inherited disorders, only SLC26A4 and SLC26A5 have been linked to hereditary hearing loss (HHL). RESULTS: Exome sequencing performed in probands from nine unrelated Moroccan families with sensorineural hearing loss identified eight SLC26A4 variants, including previously reported and novel variants, as well as a homozygous canonical splice-site variant in SLC26A5 (c.1311 + 1G > T). Sanger sequencing confirmed co-segregation of all identified variants, and in silico prediction tools consistently supported their pathogenicity. Molecular dynamics simulations performed on three SLC26A4 missense variants (p. Ser353Ala, p. Phe555Cys, and p. Leu582Pro) indicated significant, state-dependent alteration in pendrin's structural stability, suggesting impaired conformational transitions required for efficient Cl⁻/HCO₃⁻ exchange. CONCLUSION: This study provides a comprehensive molecular characterization of SLC26A4- and SLC26A5-related hearing loss in Moroccan families and significantly expands the mutational landscape of hereditary hearing loss in North Africa.