Characterization of a new full length <it>TMPRSS3 </it>isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan
<p>Abstract</p> <p>Background</p> <p>Mutant alleles of <it>TMPRSS3 </it>are associated with nonsyndromic recessive deafness (DFNB8/B10). TMPRSS3 encodes a predicted secreted serine protease, although the deduced amino acid sequence has no signal peptide. In...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2004-09-01
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| Series: | BMC Medical Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2350/5/24 |
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| author | Shotland Lawrence I Ploplis Barbara MacLaren Linda Dhillon Kiran Luscombe Sandra Ahmad Zahoor Ramzan Khushnooda Young Terry-Lynn Riazuddin Saima Powell Shontell D Cindy Li Xiaoyan Ahmed Zubair M Ives Elizabeth Riazuddin Sheikh Friedman Thomas B Morell Robert J Wilcox Edward R |
| author_facet | Shotland Lawrence I Ploplis Barbara MacLaren Linda Dhillon Kiran Luscombe Sandra Ahmad Zahoor Ramzan Khushnooda Young Terry-Lynn Riazuddin Saima Powell Shontell D Cindy Li Xiaoyan Ahmed Zubair M Ives Elizabeth Riazuddin Sheikh Friedman Thomas B Morell Robert J Wilcox Edward R |
| author_sort | Shotland Lawrence I |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Mutant alleles of <it>TMPRSS3 </it>are associated with nonsyndromic recessive deafness (DFNB8/B10). TMPRSS3 encodes a predicted secreted serine protease, although the deduced amino acid sequence has no signal peptide. In this study, we searched for mutant alleles of <it>TMPRSS3 </it>in families from Pakistan and Newfoundland with recessive deafness co-segregating with DFNB8/B10 linked haplotypes and also more thoroughly characterized the genomic structure of <it>TMPRSS3</it>.</p> <p>Methods</p> <p>We enrolled families segregating recessive hearing loss from Pakistan and Newfoundland. Microsatellite markers flanking the TMPRSS3 locus were used for linkage analysis. DNA samples from participating individuals were sequenced for <it>TMPRSS3</it>. The structure of <it>TMPRSS3 </it>was characterized bioinformatically and experimentally by sequencing novel cDNA clones of <it>TMPRSS3</it>.</p> <p>Results</p> <p>We identified mutations in <it>TMPRSS3 </it>in four Pakistani families with recessive, nonsyndromic congenital deafness. We also identified two recessive mutations, one of which is novel, of <it>TMPRSS3 </it>segregating in a six-generation extended family from Newfoundland. The spectrum of <it>TMPRSS3 </it>mutations is reviewed in the context of a genotype-phenotype correlation. Our study also revealed a longer isoform of <it>TMPRSS3 </it>with a hitherto unidentified exon encoding a signal peptide, which is expressed in several tissues.</p> <p>Conclusion</p> <p>Mutations of <it>TMPRSS3 </it>contribute to hearing loss in many communities worldwide and account for 1.8% (8 of 449) of Pakistani families segregating congenital deafness as an autosomal recessive trait. The newly identified <it>TMPRSS3 </it>isoform <it>e </it>will be helpful in the functional characterization of the full length protein.</p> |
| first_indexed | 2024-12-19T20:19:53Z |
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| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-19T20:19:53Z |
| publishDate | 2004-09-01 |
| publisher | BMC |
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| series | BMC Medical Genetics |
| spelling | doaj.art-05a0676230e64840b0aedb1c786310a42022-12-21T20:07:02ZengBMCBMC Medical Genetics1471-23502004-09-01512410.1186/1471-2350-5-24Characterization of a new full length <it>TMPRSS3 </it>isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and PakistanShotland Lawrence IPloplis BarbaraMacLaren LindaDhillon KiranLuscombe SandraAhmad ZahoorRamzan KhushnoodaYoung Terry-LynnRiazuddin SaimaPowell Shontell DCindy Li XiaoyanAhmed Zubair MIves ElizabethRiazuddin SheikhFriedman Thomas BMorell Robert JWilcox Edward R<p>Abstract</p> <p>Background</p> <p>Mutant alleles of <it>TMPRSS3 </it>are associated with nonsyndromic recessive deafness (DFNB8/B10). TMPRSS3 encodes a predicted secreted serine protease, although the deduced amino acid sequence has no signal peptide. In this study, we searched for mutant alleles of <it>TMPRSS3 </it>in families from Pakistan and Newfoundland with recessive deafness co-segregating with DFNB8/B10 linked haplotypes and also more thoroughly characterized the genomic structure of <it>TMPRSS3</it>.</p> <p>Methods</p> <p>We enrolled families segregating recessive hearing loss from Pakistan and Newfoundland. Microsatellite markers flanking the TMPRSS3 locus were used for linkage analysis. DNA samples from participating individuals were sequenced for <it>TMPRSS3</it>. The structure of <it>TMPRSS3 </it>was characterized bioinformatically and experimentally by sequencing novel cDNA clones of <it>TMPRSS3</it>.</p> <p>Results</p> <p>We identified mutations in <it>TMPRSS3 </it>in four Pakistani families with recessive, nonsyndromic congenital deafness. We also identified two recessive mutations, one of which is novel, of <it>TMPRSS3 </it>segregating in a six-generation extended family from Newfoundland. The spectrum of <it>TMPRSS3 </it>mutations is reviewed in the context of a genotype-phenotype correlation. Our study also revealed a longer isoform of <it>TMPRSS3 </it>with a hitherto unidentified exon encoding a signal peptide, which is expressed in several tissues.</p> <p>Conclusion</p> <p>Mutations of <it>TMPRSS3 </it>contribute to hearing loss in many communities worldwide and account for 1.8% (8 of 449) of Pakistani families segregating congenital deafness as an autosomal recessive trait. The newly identified <it>TMPRSS3 </it>isoform <it>e </it>will be helpful in the functional characterization of the full length protein.</p>http://www.biomedcentral.com/1471-2350/5/24 |
| spellingShingle | Shotland Lawrence I Ploplis Barbara MacLaren Linda Dhillon Kiran Luscombe Sandra Ahmad Zahoor Ramzan Khushnooda Young Terry-Lynn Riazuddin Saima Powell Shontell D Cindy Li Xiaoyan Ahmed Zubair M Ives Elizabeth Riazuddin Sheikh Friedman Thomas B Morell Robert J Wilcox Edward R Characterization of a new full length <it>TMPRSS3 </it>isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan BMC Medical Genetics |
| title | Characterization of a new full length <it>TMPRSS3 </it>isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan |
| title_full | Characterization of a new full length <it>TMPRSS3 </it>isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan |
| title_fullStr | Characterization of a new full length <it>TMPRSS3 </it>isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan |
| title_full_unstemmed | Characterization of a new full length <it>TMPRSS3 </it>isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan |
| title_short | Characterization of a new full length <it>TMPRSS3 </it>isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan |
| title_sort | characterization of a new full length it tmprss3 it isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in newfoundland and pakistan |
| url | http://www.biomedcentral.com/1471-2350/5/24 |
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