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

Xue Zhong 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

doi:10.1093/hmg/ddg127

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

Journal article

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

Xue Zhong 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, …

Human molecular genetics, Vol.12(10), pp.1155-1162

05/15/2003

DOI: 10.1093/hmg/ddg127

PMID: 12719379

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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.

Anion Transport Proteins

Alternative Splicing

Humans

Molecular Sequence Data

Male

Sequence Analysis, DNA

Sulfate Transporters

Hearing Loss - genetics

Proteins - genetics

Sequence Analysis, Protein

Hearing Loss - metabolism

Proteins - metabolism

Pedigree

Protein Isoforms

Female

Details

Title: Subtitle: Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss
Creators: Xue Zhong Liu - Department of Otolaryngology, University of Miami, Miami, FL 33101, USA. xliu@med.miami.edu
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
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.12(10), pp.1155-1162
DOI: 10.1093/hmg/ddg127
PMID: 12719379
NLM abbreviation: Hum Mol Genet
ISSN: 0964-6906
eISSN: 1460-2083
Publisher: England
Grant note: DC00089 / NIDCD NIH HHS DC02842 / NIDCD NIH HHS DC02281 / NIDCD NIH HHS DC 05575 / NIDCD NIH HHS DC04546 / NIDCD NIH HHS
Language: English
Date published: 05/15/2003
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006426202771

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