A newly identified mutation (c.2029 C > T) in SLC26A4 gene is associated with enlarged vestibular aqueducts in a Chinese family

BACKGROUND: The enlarged vestibular aqueduct (EVA), associated with mutations in the SLC26A4 gene, characterized by non-syndromic hearing loss, is an autosomal recessive disorder. Here, we intended to investigate genetic causes of hearing loss in a Han Chinese man. METHOD: First, whole-exome sequencing was performed to identify the gene mutations responsible for hearing loss in the proband. Sanger sequencing was used to verify the candidate mutations detected in the family. Next, we collected blood samples and clinical data from the three-generation pedigree. Finally, SLC26A4 mRNA and protein expression levels were detected by qPCR and western blotting. RESULT: The proband suffered from bilateral progressive sensorineural hearing loss with EVA. The sequence analysis of SLC26A4 revealed that the proband and his sister both harbored a compound heterozygous mutation of c.2168A > G/c.2029C > T, inherited from their father and mother respectively. c.2029C > T mutation has not been recorded in the relevant literature previously. Relative mRNA levels of the SLC26A4 gene in individuals carrying a compound heterozygous mutation were significantly lower compared to a heterozygous mutation. SLC26A4 protein levels of 293t cells which transfected with recombinant plasmids [GV219-SLC26A4-mut (c.2029C > T) and GV219-SLC26A4-mut (c.2168A > G/c.2029C > T)] were significantly lower than normal control recombinant plasmids (GV219-SLC26A4-wt). CONCLUSION: This study found a novel heterozygous mutation c.2029 (exon17) C > T compound with c.2168 (exon19) A > G in the SLC26A4 gene in a patient with EVA. The c.2029 (exon17) C > T mutation is proved to be pathogenic. This finding broadens the spectrum of variants in SLC26A4 gene. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01200-4.