A new mutation in the human pres gene and its effect on prestin function

  • Authors:
    • Timea Toth
    • Levente Deak
    • Ferenc Fazakas
    • Jing Zheng
    • Laszlo Muszbek
    • Istvan Sziklai
  • View Affiliations

  • Published online on: October 1, 2007     https://doi.org/10.3892/ijmm.20.4.545
  • Pages: 545-550
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Abstract

The electromotility of cochlear outer hair cells (OHCs) is a major factor in cochlear amplification that enhances the sensitivity of hearing in humans. Prestin is associated with presumed conformational changes in an integral membrane protein. Prestin knockout (−/−) mice display loss of OHC electromotility and a 40- to 60-dB reduction in cochlear sensitivity in vivo. In the present study we described the results of a direct sequencing mutation in the pres gene that was found in genetic screening performed in 47 patients characterized by non-syndromic, mild-to-moderate hearing impairment (30-70 dB) and in 50 control subjects from Hungary, after exclusion of GJB (GJB2, GJB6) mutations in the background. Only one patient and his normal-hearing father showed a heterozygous missense mutation (R150Q/WT) in the 6th coding exon of the pres gene. None of the 50 control subjects with normal hearing carried this mutation. Electrophysiological studies on the R150Q (homozygous and heterozygous) prestin mutant transiently transfected into reporting cells demonstrated nonlinear capacitance functions (NLC) as a signature of OHC electromotility. The capacitance function in human kidney cell line TSA 201 was similar for wild-type prestin and the mutant. However, for the mutant the voltage where the maximal charge displacement occurred (V1/2) significantly shifted in the hyperpolarizing direction (≈15 mV). This is the first genetic and electrophysiological analysis of a human mutation in a coding exon of the pres gene by 47 patients with non-syndromic, sensorineural, mild-to-moderate hearing impairment; although the pathogenic role of the R150Q mutation is not unambiguous.

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October 2007
Volume 20 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Toth T, Deak L, Fazakas F, Zheng J, Muszbek L and Sziklai I: A new mutation in the human pres gene and its effect on prestin function. Int J Mol Med 20: 545-550, 2007
APA
Toth, T., Deak, L., Fazakas, F., Zheng, J., Muszbek, L., & Sziklai, I. (2007). A new mutation in the human pres gene and its effect on prestin function. International Journal of Molecular Medicine, 20, 545-550. https://doi.org/10.3892/ijmm.20.4.545
MLA
Toth, T., Deak, L., Fazakas, F., Zheng, J., Muszbek, L., Sziklai, I."A new mutation in the human pres gene and its effect on prestin function". International Journal of Molecular Medicine 20.4 (2007): 545-550.
Chicago
Toth, T., Deak, L., Fazakas, F., Zheng, J., Muszbek, L., Sziklai, I."A new mutation in the human pres gene and its effect on prestin function". International Journal of Molecular Medicine 20, no. 4 (2007): 545-550. https://doi.org/10.3892/ijmm.20.4.545