Unique SLC26A4 Mutation Spectrum in Mongolian Patients with Enlarged Vestibular Aqueduct: A Whole-Exome Sequencing Study

Background: Enlarged vestibular aqueduct (EVA) is a common inner ear malformation that can cause sensorineural hearing loss. It is frequently associated with mutations in the SLC26A4 gene. This study aimed to investigate the genetic basis of hearing loss in Mongolian patients with EVA. Methods: Whole exome sequencing was performed in 19 Mongolian patients from 15 unrelated families diagnosed with EVA with/without cochlear incomplete partition type II. All patients underwent high-resolution computed tomography of the temporal bone to confirm the diagnosis. Results: Biallelic SLC26A4 pathogenic variants were identified in all 15 families (100%). The most frequent variant was c.919-2A>G (40%), followed by c.2027T>A (23.3%) and c.1318A>T (16.7%). Population-specific variants in East Asians (c.919-2A>G), North Asians (c.2027T>A), and Southwest Asians (c.716T>A) were all present in Mongolian patients, demonstrating a pan-ethnic mutation spectrum. Digenic inheritance was not observed. There was no clear genotype-phenotype correlation between specific SLC26A4 genotypes and hearing levels or inner ear malformations. Conclusions: This study provides a comprehensive overview of the genetic landscape of EVA in the Mongolian population. The identification of biallelic SLC26A4 pathogenic variants in all families highlights the importance of this gene in the pathogenesis of EVA. The unique mutation spectrum observed in this study may reflect the genetic diversity resulting from historical migrations of Mongolians. Keywords: Sensorineural hearing loss, enlarged vestibular aqueducts, cochlear incomplete partition, whole exome sequencing, DFNB4, SLC26A4