Prevalent SLC26A4 mutations in patients with enlarged vestibular aqueduct and/or Mondini dysplasia: a unique spectrum of mutations in Taiwan, including a frequent founder mutation.

OBJECTIVES/HYPOTHESIS: The purpose of the study is to elucidate the mutation spectrum of SLC26A4 among patients with enlarged vestibular aqueduct and/or Mondini dysplasia in Taiwan and to explore the origin of the most common mutation, IVS7-2A>G. The correlation between the genotypes and the phenotypes is also investigated, with special emphasis placed on comparison between the genotypes and hearing levels.

STUDY DESIGN: A 3-year prospective clinical genetic study at a tertiary care university hospital.

METHOD: Mutations on SLC26A4 were screened in 38 families that fulfilled the criteria of enrollment, and single nucleotide polymorphisms (SNPs) in the vicinity of IVS7-2A>G were typed. The presence of goiter, radiologic findings, and audiologic results of the probands were then compared according to the genotypes.

RESULTS: A total of eight mutations were detected in 33 families, and IVS7-2A>G accounted for 84% (48/57) of the mutated alleles. SNP analysis confirmed the founder effect of IVS7-2A>G. Meanwhile, no obvious correlation was observed between SLC26A4 genotypes and phenotypes.

CONCLUSION: The present study disclosed the unique SLC26A4 mutation spectrum in Taiwan, confirmed that IVS7-2A>G arose from a common ancestor, and demonstrated the lack of correlation between genotypes and phenotypes. High prevalence of certain SLC26A4 mutations in East Asians, as revealed here and previously, might largely facilitate mutation screening and genetic counseling in these areas.