Using T7 endonuclease I to detect SLC26A4 mutations in children with large vestibular aqueduct syndrome, with or without Mondini malformation and assess cochlear implant outcomes.

Objective: To analyze SLC26A4 gene mutations in children with large vestibular aqueduct syndrome (LVAS) with or without Mondini malformation, and to compare their hearing phenotypes, rehabilitation outcomes, and learning performance after cochlear implantation.

Methods: We used T7 Endonuclease I enzyme digestion to detect SLC26A4 mutations in 48 children with LVAS without Mondini malformation (EVA group), 29 children with LVAS and Mondini malformation (EVA + MD group). Negative results were confirmed by Sanger sequencing. Auditory performance (CAP) and speech intelligibility (SIR) scores assessed hearing and speech rehabilitation outcomes, while academic performance evaluated learning post-cochlear implantation.

Results: Electrophoresis showed that the positive detection rates of SLC26A4 mutations were 89.58% in the EVA group, 89.66% in the EVA + MD group, and 0% in the control group. In the EVA group, the most common mutations were in exons 7 + 8 (52.08%), 11 + 12 (22.92%), and 19 (18.75%). In the EVA + MD group, the predominant mutations were in exons 11 + 12 (51.72%), 4 (34.48%), 7 + 8 (27.59%), and 19 (24.14%). The EVA + MD group had higher detection rates for two-site (37.93%) and three-site compound heterozygous mutations (13.79%) compared to the EVA group (22.92% and 10.42%, respectively). The median diagnosis time for profound hearing loss was 6.62 months in the EVA + MD group versus 10.56 months in the EVA group. There were no significant differences in CAP and SIR scores between the groups, but the EVA group showed better learning performance.

Conclusion: This study reports, for the first time, multiple cases exhibiting a three-site compound heterozygous mutation in the SLC26A4 gene. The hotspot exons of the SLC26A4 gene differ between children with simple LVAS and those with LVAS accompanied by Mondini malformation. Children with both conditions show earlier onset of profound hearing loss and poorer learning performance compared to those with only LVAS.