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

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, t...

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Published in:Human molecular genetics 2003-05, Vol.12 (10), p.1155-1162
Main Authors: Liu, Xue Zhong, 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
Format: Article
Language:English
Subjects:
Alternative Splicing
Anion Transport Proteins
Biological and medical sciences
Female
Fundamental and applied biological sciences. Psychology
Hearing Loss - genetics
Hearing Loss - metabolism
Humans
Male
Molecular and cellular biology
Molecular Sequence Data
Pedigree
Protein Isoforms
Proteins - genetics
Proteins - metabolism
Sequence Analysis, DNA
Sequence Analysis, Protein
Sulfate Transporters
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Summary: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.
ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/ddg127