Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss

Xue Z Liu, Xiao Mei Ouyang, Xia Juan Xia, Jing Zheng, Arti Pandya, Fang Li, Li Lin Du, Katherine O. Welch, Christine Petit, Richard J H Smith, Bradley T. Webb, Denise Yan, Kathleen S. Arnos, David Corey, Peter Dallos, Walter E. Nance, Zheng Yi Chen

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Abstract

Prestin, a membrane protein that is highly and almost exclusively expressed in the outer hair cells (OHCs) of the cochlea, is a motor protein which senses membrane potential and drives rapid length changes in OHCs. Surprisingly, prestin is a member of a gene family, solute carrier (SLC) family 26, that encodes anion transporters and related proteins. Of nine known human genes in this family, three (SLC26A2, SLC26A3 and SLC26A4) are associated with different human hereditary diseases. The restricted expression of prestin in OHCs, and its proposed function as a mechanical amplifier, make it a strong candidate gene for human deafness. Here we report the cloning and characterization of four splicing isoforms for the human prestin gene (SLC26A5a, b, c and d). SLC26A5a is the predominant form of prestin whereas the others showed limited distribution associated with certain developmental stages. Based on the functional importance of prestin we screened for possible mutations involving the prestin gene in a group of deaf probands. We have identified a 5′-UTR splice acceptor mutation (IVS2-2A>G) in exon 3 of the prestin gene, which is responsible for recessive non-syndromic deafness in two unrelated families. In addition, a high frequency of heterozygosity for the same mutation was observed in these subjects, suggesting the possibility of semi-dominant influence of the mutation in causing hearing loss. Finally, the observation of this mutation only in the Caucasian probands indicated an association with a specific ethnic background. This study thereby reveals an essential function of prestin in human auditory processing.

Original languageEnglish
Pages (from-to)1155-1162
Number of pages8
JournalHuman Molecular Genetics
Volume12
Issue number10
DOIs
StatePublished - May 15 2003

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Cochlea
Hearing Loss
Outer Auditory Hair Cells
Mutation
Genes
Proteins
Deafness
Inborn Genetic Diseases
5' Untranslated Regions
Membrane Potentials
Anions
Organism Cloning
Exons
Protein Isoforms
Membrane Proteins
Observation

ASJC Scopus subject areas

  • Genetics

Cite this

Liu, X. Z., Ouyang, X. M., Xia, X. J., Zheng, J., Pandya, A., Li, F., ... Chen, Z. Y. (2003). Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. Human Molecular Genetics, 12(10), 1155-1162. https://doi.org/10.1093/hmg/ddg127

Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. / Liu, Xue Z; Ouyang, Xiao Mei; Xia, Xia Juan; Zheng, Jing; Pandya, Arti; Li, Fang; Du, Li Lin; Welch, Katherine O.; Petit, Christine; Smith, Richard J H; Webb, Bradley T.; Yan, Denise; Arnos, Kathleen S.; Corey, David; Dallos, Peter; Nance, Walter E.; Chen, Zheng Yi.

In: Human Molecular Genetics, Vol. 12, No. 10, 15.05.2003, p. 1155-1162.

Research output: Contribution to journalArticle

Liu, XZ, Ouyang, XM, Xia, XJ, Zheng, J, Pandya, A, Li, F, Du, LL, Welch, KO, Petit, C, Smith, RJH, Webb, BT, Yan, D, Arnos, KS, Corey, D, Dallos, P, Nance, WE & Chen, ZY 2003, 'Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss', Human Molecular Genetics, vol. 12, no. 10, pp. 1155-1162. https://doi.org/10.1093/hmg/ddg127
Liu, Xue Z ; Ouyang, Xiao Mei ; Xia, Xia Juan ; Zheng, Jing ; Pandya, Arti ; Li, Fang ; Du, Li Lin ; Welch, Katherine O. ; Petit, Christine ; Smith, Richard J H ; Webb, Bradley T. ; Yan, Denise ; Arnos, Kathleen S. ; Corey, David ; Dallos, Peter ; Nance, Walter E. ; Chen, Zheng Yi. / Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. In: Human Molecular Genetics. 2003 ; Vol. 12, No. 10. pp. 1155-1162.
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T1 - Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss

AU - Liu, Xue Z

AU - Ouyang, Xiao Mei

AU - Xia, Xia Juan

AU - Zheng, Jing

AU - Pandya, Arti

AU - Li, Fang

AU - Du, Li Lin

AU - Welch, Katherine O.

AU - Petit, Christine

AU - Smith, Richard J H

AU - Webb, Bradley T.

AU - Yan, Denise

AU - Arnos, Kathleen S.

AU - Corey, David

AU - Dallos, Peter

AU - Nance, Walter E.

AU - Chen, Zheng Yi

PY - 2003/5/15

Y1 - 2003/5/15

N2 - Prestin, a membrane protein that is highly and almost exclusively expressed in the outer hair cells (OHCs) of the cochlea, is a motor protein which senses membrane potential and drives rapid length changes in OHCs. Surprisingly, prestin is a member of a gene family, solute carrier (SLC) family 26, that encodes anion transporters and related proteins. Of nine known human genes in this family, three (SLC26A2, SLC26A3 and SLC26A4) are associated with different human hereditary diseases. The restricted expression of prestin in OHCs, and its proposed function as a mechanical amplifier, make it a strong candidate gene for human deafness. Here we report the cloning and characterization of four splicing isoforms for the human prestin gene (SLC26A5a, b, c and d). SLC26A5a is the predominant form of prestin whereas the others showed limited distribution associated with certain developmental stages. Based on the functional importance of prestin we screened for possible mutations involving the prestin gene in a group of deaf probands. We have identified a 5′-UTR splice acceptor mutation (IVS2-2A>G) in exon 3 of the prestin gene, which is responsible for recessive non-syndromic deafness in two unrelated families. In addition, a high frequency of heterozygosity for the same mutation was observed in these subjects, suggesting the possibility of semi-dominant influence of the mutation in causing hearing loss. Finally, the observation of this mutation only in the Caucasian probands indicated an association with a specific ethnic background. This study thereby reveals an essential function of prestin in human auditory processing.

AB - Prestin, a membrane protein that is highly and almost exclusively expressed in the outer hair cells (OHCs) of the cochlea, is a motor protein which senses membrane potential and drives rapid length changes in OHCs. Surprisingly, prestin is a member of a gene family, solute carrier (SLC) family 26, that encodes anion transporters and related proteins. Of nine known human genes in this family, three (SLC26A2, SLC26A3 and SLC26A4) are associated with different human hereditary diseases. The restricted expression of prestin in OHCs, and its proposed function as a mechanical amplifier, make it a strong candidate gene for human deafness. Here we report the cloning and characterization of four splicing isoforms for the human prestin gene (SLC26A5a, b, c and d). SLC26A5a is the predominant form of prestin whereas the others showed limited distribution associated with certain developmental stages. Based on the functional importance of prestin we screened for possible mutations involving the prestin gene in a group of deaf probands. We have identified a 5′-UTR splice acceptor mutation (IVS2-2A>G) in exon 3 of the prestin gene, which is responsible for recessive non-syndromic deafness in two unrelated families. In addition, a high frequency of heterozygosity for the same mutation was observed in these subjects, suggesting the possibility of semi-dominant influence of the mutation in causing hearing loss. Finally, the observation of this mutation only in the Caucasian probands indicated an association with a specific ethnic background. This study thereby reveals an essential function of prestin in human auditory processing.

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