Human Genetics

, Volume 122, Issue 5, pp 451–457 | Cite as

Genotype–phenotype correlations for SLC26A4-related deafness

  • Hela Azaiez
  • Tao Yang
  • Sai Prasad
  • Jessica L. Sorensen
  • Carla J. Nishimura
  • William J. Kimberling
  • Richard J. H. SmithEmail author
Original Investigation


Pendred syndrome (PS) and non-syndromic enlarged vestibular aqueduct (EVA) are two recessive disorders characterized by the association of sensorineural hearing loss (SNHL) with inner ear malformations that range from isolated EVA to Mondini Dysplasia, a complex malformation that includes a cochlear dysplasia and EVA. Mutations in the SLC26A4 gene, coding for the protein pendrin, have been implicated in the pathophysiology of both disorders. In order to determine whether SLC26A4 genotypes can be correlated to the complexity and severity of the phenotypes, we ascertained 1,506 deaf patients. Inner ear abnormalities were present in 474 patients (32%). Mutation screening of SLC26A4 detected two mutations in 16% of patients, one mutation in 19% of patients and zero mutation in 65% of patients. When the distribution of SLC26A4 genotypes was compared across phenotypes, a statistically significant difference was found between PS patients and non-syndromic EVA–Mondini patients (P = 0.005), as well as between EVA patients and Mondini patients (P = 0.0003). There was a correlation between phenotypic complexity of inner ear malformations and genetic heterogeneity—PS patients have the most severe phenotype and the most homogeneous etiology while EVA patients have the least severe phenotype and the most heterogeneous etiology. For all patients, variability in the degree of hearing loss is seen across genotypes implicating other genetic and/or environmental factors in the pathogenesis of the PS–Mondini–EVA disease spectrum.


Hearing Loss Goiter SLC26A4 Gene Multiplex Family SLC26A4 Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank the study patients and families for their participation in this study, which was supported in part by a grant from the NIDCD (R01-DC02842) to RJHS.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Hela Azaiez
    • 1
    • 2
    • 3
  • Tao Yang
    • 1
  • Sai Prasad
    • 1
  • Jessica L. Sorensen
    • 1
  • Carla J. Nishimura
    • 1
  • William J. Kimberling
    • 4
  • Richard J. H. Smith
    • 1
    • 2
    Email author
  1. 1.Molecular Otolaryngology Research Laboratories, Department of Otolaryngology-Head and Neck SurgeryUniversity of Iowa Hospitals and ClinicsIowa CityUSA
  2. 2.Interdepartmental PhD Program in GeneticsUniversity of Iowa Hospitals and ClinicsIowa CityUSA
  3. 3.Laboratoire de Génétique Moléculaire HumaineFaculté de Médecine de SfaxSfaxTunisia
  4. 4.Boys Town National Research HospitalOmahaUSA

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