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

Abstract 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.