A novel missense mutation in the SLC26A4 gene causes nonsyndromic hearing loss and enlarged vestibular aqueduct.

Objectives: We aimed to investigate the genetic causes of hearing loss in a Chinese proband with nonsyndromic hearing loss and enlarged vestibular aqueduct syndrome.

Methods: We conducted clinical and genetic evaluations in a deaf proband and his normal-hearing parents. Multiplex PCR technology combined with Ion Torrent™ next-generation sequencing technology was used to detect the pathogenic mutations. As a control, a group of 1500 previously studied healthy newborns from the same ethnic background were subjected to deafness gene screening using the same method as in our previous study.

Results: The proband harbored two mutations in the SLC26A4 gene in the form of compound heterozygosity. He was found to be heterozygous for a novel mutation named c.1742 G > T (p.Arg581Met) in exon 13 and for the known mutation c.589 G > A (p.Gly197Arg). These variants were carried in the heterozygous state by the parents and therefore co-segregated with the genetic disease. The c.1742 G > T (p.Arg581Met) mutation was absent in 1500 healthy newborns. Protein alignment indicated high evolutionary conservation of the p.R581 residue, and this mutation was predicted by PolyPhen-2 and other online tools to be damaging.

Conclusion: This study demonstrates that the novel mutation c.1742 G > T (p.Arg581Met) in compound heterozygosity with c.589 G > A in the SLC26A4 gene is the main cause of deafness in a family clinically diagnosed with enlarged vestibular aqueduct (EVA). Our study will provide a basic foundation for further investigations to elucidate the SLC26A4-related mechanisms of hearing loss.