Novel compound heterozygous mutations in SLC26A4 gene in a Chinese Han family with enlarged vestibular aqueduct

ObjectiveTo identify the disease-related SLC26A4 mutants in a Chinese Han pedigree associated with Enlarged vestibular aqueduct (EVA).MethodsEVA diagnosis was based on the family history, clinical examinations, systematically audiometric evaluations, high-resolution computed tomography (HRCT) of the temporal bone, and magnetic resonance imaging (MRI) of inner ear. Sanger sequencing and mutation analysis of the SLC26A4 gene were performed in all members of this family to identify the disease-related SLC26A4 mutants. Mutations in the SLC26A4 gene were compared with 200 ethnically matched control persons to exclude common polymorphism.ResultsAll members in this family were negative for systemic and thyroid diseases. There were three subjects (I-2, II-2 and II-3) with bilateral sensorineural deafness since childhood. Temporal bone HRCT scans and inner ear MRI showed bilateral enlarged vestibular aqueduct with Mondini malformation in II-2 and II-3. A novel SLC26A4 splice-site mutation c.1001 + 5G > C was identified in compound heterozygosity with the mutation c.919-2A > G in the proband and in II-2. This novel compound heterozygote of two splice site mutations was not found in 200 normal hearing Chinese Han controls.ConclusionsA novel splice site mutation of c.1001 + 5G > C was identified, and the novel compound heterozygote of two splice site mutations, c.1001 + 5G > C and c.919-2A > G, in the SLC26A4 gene has been linked to hearing impairment in EVA patients.