Mutation Analysis of Slc26a4

OBJECTIVE: We have characterized the spectrum of SLC26A4 mutations and clinical features in a mainland Chinese population with sensorineural non syndromic hearing loss (SNHL) and enlarged vestibular aqueduct (EVA). STUDY DESIGN: Cross-sectional clinical genetic study. SETTING: Tertiary care outpatient otolaryngology clinic. METHODS: 32 subjects identified with bilateral EVA using high resolution computed tomography (CT) were screened for mutations in SLC26A4 by denaturing high-performance liquid chromatography (DPHLC) and direct sequencing methods. RESULTS: A total of thirteen different mutations were identified in the SLC26A4 gene, five of which are novel. A total of 88% of the patients harbored biallelic mutations, eleven patients were homozygotes, and seventeen were compound heterozygotes. Four patients were found to carry a single SLC26A4 mutation. The IVS7-2A>G mutation was the most frequent, accounting for 60% of the mutant alleles. We have not found any correlations between the type of SLC26A4 mutations and the type, degree and progression of hearing loss. There are significant proportions of patients with asymmetric (26%), progressive (32%), or fluctuating hearing loss (21%). CONCLUSION: Our data confirm the high prevalence of SLC26A4 mutations in Chinese patients with sensorineural hearing loss (SNHL) and EVA. We could not establish any relationship between genotype and phenotype. However, high incidence of asymmetric, progressive, and fluctuating hearing loss found in the current study indicates that patients with those features should be routinely screened for SLC26A4 mutation in addition to diagnosis of EVA using CT or magnetic resonance imaging