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

Erdenechuluun, J.; Gombojav, B.; Batsaikan, T.; Lu, Y.-S.; Danshiitsoodol, N.; Makhbal, Z.; Jargalmaa, M.; Jargalkhuu, T.; Hsu, H.-P.; Lin, P.-H.; Su, H.-J.; Lin, C.-H.; Hsu, C.-J.; Chen, P.-L.; Tsai, C.-Y.; Wu, C.-C.

2025-02-05 genetic and genomic medicine
10.1101/2025.02.03.25321220 medRxiv
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BackgroundEnlarged 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. MethodsWhole 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. ResultsBiallelic 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 panethnic 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. ConclusionsThis 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.

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