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. Smith

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)451-457
Number of pages7
JournalHuman genetics
Volume122
Issue number5
DOIs
StatePublished - Dec 1 2007

Fingerprint

Genetic Association Studies
Deafness
Inner Ear
Mutation
Phenotype
Genotype
Vestibular Diseases
Genetic Heterogeneity
Sensorineural Hearing Loss
Cochlea
Enlarged Vestibular Aqueduct
Hearing Loss

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Azaiez, H., Yang, T., Prasad, S., Sorensen, J. L., Nishimura, C. J., Kimberling, W. J., & Smith, R. J. H. (2007). Genotype-phenotype correlations for SLC26A4- related deafness. Human genetics, 122(5), 451-457. https://doi.org/10.1007/s00439-007-0415-2

Genotype-phenotype correlations for SLC26A4- related deafness. / Azaiez, Hela; Yang, Tao; Prasad, Sai; Sorensen, Jessica L.; Nishimura, Carla J.; Kimberling, William J; Smith, Richard J.H.

In: Human genetics, Vol. 122, No. 5, 01.12.2007, p. 451-457.

Research output: Contribution to journalArticle

Azaiez, H, Yang, T, Prasad, S, Sorensen, JL, Nishimura, CJ, Kimberling, WJ & Smith, RJH 2007, 'Genotype-phenotype correlations for SLC26A4- related deafness', Human genetics, vol. 122, no. 5, pp. 451-457. https://doi.org/10.1007/s00439-007-0415-2
Azaiez H, Yang T, Prasad S, Sorensen JL, Nishimura CJ, Kimberling WJ et al. Genotype-phenotype correlations for SLC26A4- related deafness. Human genetics. 2007 Dec 1;122(5):451-457. https://doi.org/10.1007/s00439-007-0415-2
Azaiez, Hela ; Yang, Tao ; Prasad, Sai ; Sorensen, Jessica L. ; Nishimura, Carla J. ; Kimberling, William J ; Smith, Richard J.H. / Genotype-phenotype correlations for SLC26A4- related deafness. In: Human genetics. 2007 ; Vol. 122, No. 5. pp. 451-457.
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