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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2009-5-15
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pubmed:abstractText |
Mutations in SLC26A4 cause nonsyndromic hearing loss associated with an enlarged vestibular aqueduct (EVA, also known as DFNB4) and Pendred syndrome (PS), the most common type of autosomal-recessive syndromic deafness. In many patients with an EVA/PS phenotype, mutation screening of SLC26A4 fails to identify two disease-causing allele variants. That a sizable fraction of patients carry only one SLC26A4 mutation suggests that EVA/PS is a complex disease involving other genetic factors. Here, we show that mutations in the inwardly rectifying K(+) channel gene KCNJ10 are associated with nonsyndromic hearing loss in carriers of SLC26A4 mutations with an EVA/PS phenotype. In probands from two families, we identified double heterozygosity in affected individuals. These persons carried single mutations in both SLC26A4 and KCNJ10. The identified SLC26A4 mutations have been previously implicated in EVA/PS, and the KCNJ10 mutations reduce K(+) conductance activity, which is critical for generating and maintaining the endocochlear potential. In addition, we show that haploinsufficiency of Slc26a4 in the Slc26a4(+/-) mouse mutant results in reduced protein expression of Kcnj10 in the stria vascularis of the inner ear. Our results link KCNJ10 mutations with EVA/PS and provide further support for the model of EVA/PS as a multigenic complex disease.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-10051166,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-10449762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-11152663,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-11466414,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-11788352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-12354788,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-12408075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-14508505,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-14679580,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-15155950,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-15297675,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-15320950,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-15350275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-15679828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-15689455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-16570074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-17299139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-17357078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-17503324,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-17690912,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-17718863,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-17942730,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-17959752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-18285825,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-18509313,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-19017801,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-19204907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-19289823,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-2813076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-6089576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-8670799,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-8951443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-9398842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-9500541,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19426954-9662649
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1537-6605
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
84
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
651-7
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:19426954-Animals,
pubmed-meshheading:19426954-Anion Transport Proteins,
pubmed-meshheading:19426954-Female,
pubmed-meshheading:19426954-Hearing Loss,
pubmed-meshheading:19426954-Heterozygote,
pubmed-meshheading:19426954-Humans,
pubmed-meshheading:19426954-Membrane Transport Proteins,
pubmed-meshheading:19426954-Mice,
pubmed-meshheading:19426954-Mice, Mutant Strains,
pubmed-meshheading:19426954-Mutation,
pubmed-meshheading:19426954-Oocytes,
pubmed-meshheading:19426954-Patch-Clamp Techniques,
pubmed-meshheading:19426954-Pedigree,
pubmed-meshheading:19426954-Potassium Channels, Inwardly Rectifying,
pubmed-meshheading:19426954-Stria Vascularis,
pubmed-meshheading:19426954-Thyroid Diseases,
pubmed-meshheading:19426954-Vestibular Aqueduct,
pubmed-meshheading:19426954-Xenopus
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pubmed:year |
2009
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pubmed:articleTitle |
Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic nonsyndromic hearing loss associated with enlarged vestibular aqueduct syndrome.
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pubmed:affiliation |
Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, PR China.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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