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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 |
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creator | 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 |
description | 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. |
doi_str_mv | 10.1093/hmg/ddg127 |
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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.</description><identifier>ISSN: 0964-6906</identifier><identifier>ISSN: 1460-2083</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddg127</identifier><identifier>PMID: 12719379</identifier><identifier>CODEN: HNGEE5</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>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</subject><ispartof>Human molecular genetics, 2003-05, Vol.12 (10), p.1155-1162</ispartof><rights>2003 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) May 15, 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-eb30671051744ef4e57b48adc55ffc26f2ee8998727e49f6df130dcc127d0ae33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14905043$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12719379$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Xue Zhong</creatorcontrib><creatorcontrib>Ouyang, Xiao Mei</creatorcontrib><creatorcontrib>Xia, Xia Juan</creatorcontrib><creatorcontrib>Zheng, Jing</creatorcontrib><creatorcontrib>Pandya, Arti</creatorcontrib><creatorcontrib>Li, Fang</creatorcontrib><creatorcontrib>Du, Li Lin</creatorcontrib><creatorcontrib>Welch, Katherine O.</creatorcontrib><creatorcontrib>Petit, Christine</creatorcontrib><creatorcontrib>Smith, Richard J.H.</creatorcontrib><creatorcontrib>Webb, Bradley T.</creatorcontrib><creatorcontrib>Yan, Denise</creatorcontrib><creatorcontrib>Arnos, Kathleen S.</creatorcontrib><creatorcontrib>Corey, David</creatorcontrib><creatorcontrib>Dallos, Peter</creatorcontrib><creatorcontrib>Nance, Walter E.</creatorcontrib><creatorcontrib>Chen, Zheng Yi</creatorcontrib><title>Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss</title><title>Human molecular genetics</title><addtitle>Hum. Mol. Genet</addtitle><description>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.</description><subject>Alternative Splicing</subject><subject>Anion Transport Proteins</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hearing Loss - genetics</subject><subject>Hearing Loss - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Pedigree</subject><subject>Protein Isoforms</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Sequence Analysis, DNA</subject><subject>Sequence Analysis, Protein</subject><subject>Sulfate Transporters</subject><issn>0964-6906</issn><issn>1460-2083</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqF0U2LFDEQBuAgijuuXvwB0gh6ENvNdzpHGdRVZlHwA9lLyCSVmazdyZr0iPvvzTCDC1485VBPinqrEHpM8CuCNTvbTpsz7zeEqjtoQbjEPcUDu4sWWEveS43lCXpQ6xXGRHKm7qOTRolmSi_QxacCdY7pZWc7l912BFu6Kc-5dNclz7CvxNp5CODm-Au6mLqUU19vki95iq7bth8xbbox1_oQ3Qt2rPDo-J6ir2_ffFme96uP794vX696Jwibe1gzLBXBgijOIXAQas0H650QITgqAwUYtB4UVcB1kD4Qhr1zbWyPLTB2ip4f-rYZf-5aADPF6mAcbYK8q0YxSpWg-L-QDIpTIVSDT_-BV3lXUgthKCFUEC5kQy8OyJUWtkAw1yVOttwYgs3-FKadwhxO0fCTY8fdegJ_S4-7b-DZEdjq7BiKTS7WW8c1Fpjvw_YHF-sMv__WbflhpGJKmPPvl2b1marlh2-X5oL9AWmsoD4</recordid><startdate>20030515</startdate><enddate>20030515</enddate><creator>Liu, Xue Zhong</creator><creator>Ouyang, Xiao Mei</creator><creator>Xia, Xia Juan</creator><creator>Zheng, Jing</creator><creator>Pandya, Arti</creator><creator>Li, Fang</creator><creator>Du, Li Lin</creator><creator>Welch, Katherine O.</creator><creator>Petit, Christine</creator><creator>Smith, Richard J.H.</creator><creator>Webb, Bradley T.</creator><creator>Yan, Denise</creator><creator>Arnos, Kathleen S.</creator><creator>Corey, David</creator><creator>Dallos, Peter</creator><creator>Nance, Walter E.</creator><creator>Chen, Zheng Yi</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030515</creationdate><title>Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-eb30671051744ef4e57b48adc55ffc26f2ee8998727e49f6df130dcc127d0ae33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Alternative Splicing</topic><topic>Anion Transport Proteins</topic><topic>Biological and medical sciences</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hearing Loss - genetics</topic><topic>Hearing Loss - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Pedigree</topic><topic>Protein Isoforms</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Sequence Analysis, DNA</topic><topic>Sequence Analysis, Protein</topic><topic>Sulfate Transporters</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Xue Zhong</creatorcontrib><creatorcontrib>Ouyang, Xiao Mei</creatorcontrib><creatorcontrib>Xia, Xia Juan</creatorcontrib><creatorcontrib>Zheng, Jing</creatorcontrib><creatorcontrib>Pandya, Arti</creatorcontrib><creatorcontrib>Li, Fang</creatorcontrib><creatorcontrib>Du, Li Lin</creatorcontrib><creatorcontrib>Welch, Katherine O.</creatorcontrib><creatorcontrib>Petit, Christine</creatorcontrib><creatorcontrib>Smith, Richard J.H.</creatorcontrib><creatorcontrib>Webb, Bradley T.</creatorcontrib><creatorcontrib>Yan, Denise</creatorcontrib><creatorcontrib>Arnos, Kathleen S.</creatorcontrib><creatorcontrib>Corey, David</creatorcontrib><creatorcontrib>Dallos, Peter</creatorcontrib><creatorcontrib>Nance, Walter E.</creatorcontrib><creatorcontrib>Chen, Zheng Yi</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Xue Zhong</au><au>Ouyang, Xiao Mei</au><au>Xia, Xia Juan</au><au>Zheng, Jing</au><au>Pandya, Arti</au><au>Li, Fang</au><au>Du, Li Lin</au><au>Welch, Katherine O.</au><au>Petit, Christine</au><au>Smith, Richard J.H.</au><au>Webb, Bradley T.</au><au>Yan, Denise</au><au>Arnos, Kathleen S.</au><au>Corey, David</au><au>Dallos, Peter</au><au>Nance, Walter E.</au><au>Chen, Zheng Yi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum. Mol. Genet</addtitle><date>2003-05-15</date><risdate>2003</risdate><volume>12</volume><issue>10</issue><spage>1155</spage><epage>1162</epage><pages>1155-1162</pages><issn>0964-6906</issn><issn>1460-2083</issn><eissn>1460-2083</eissn><coden>HNGEE5</coden><notes>istex:989DA087CE383773F1C82550456FF392BA846B29</notes><notes>ark:/67375/HXZ-LS27CJVZ-M</notes><notes>local:ddg127</notes><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>12719379</pmid><doi>10.1093/hmg/ddg127</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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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 |
title | Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss |
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