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http://purl.uniprot.org/citations/21242547http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21242547http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21242547http://www.w3.org/2000/01/rdf-schema#comment"

Objective

To identify the genetic etiology in a family with autosomal dominant progressive sensorineural hearing loss.

Design

Prospective molecular genetic research study.

Setting

Academic genetic research laboratory.

Participants

Seventeen members of a family with dominant progressive nonsyndromic sensorineural hearing loss: 9 affected, 6 unaffected, and 2 spouses.

Interventions

Clinical data from questionnaires, interviews, serial audiograms, and medical records; genetic data from genome-wide linkage analysis and candidate gene mutation analysis.

Main outcome measures

Symptoms, age at onset, serial audiometric data, and the presence or absence of a deafness-associated mutation.

Results

Affected individuals in this family presented with autosomal dominant nonsyndromic high-frequency progressive sensorineural hearing loss, with age at onset ranging from 1 to 21 years. Genome-wide linkage analysis of single-nucleotide polymorphisms yielded evidence of linkage to an 18.9-Mb region on chromosome 1p34-p36, with a multipoint logarithm of odds score of 3.6. This interval contains a known deafness gene, KCNQ4, which underlies DNFA2 deafness. Sequencing of the 14 coding exons and intron-exon junctions of KCNQ4 revealed a novel heterozygous missense mutation, c.859G>C, p.Gly287Arg. The mutation disrupts the highly conserved GYG motif (glycine-tyrosine-glycine) of the phosphate-binding loop, hypothesized to be critical in maintaining pore structure and function. All 274 controls were negative for the mutation.

Conclusions

Autosomal dominant high-frequency hearing loss is genetically heterogeneous, and linkage analysis is an efficient means of identifying the etiology in larger families. Deafness in this family is caused by a novel mutation in KCNQ4."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.org/dc/terms/identifier"doi:10.1001/archoto.2010.234"xsd:string
http://purl.uniprot.org/citations/21242547http://purl.org/dc/terms/identifier"doi:10.1001/archoto.2010.234"xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Lee K."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Lee K."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Leal S.M."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Leal S.M."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Arnett J."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Arnett J."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Emery S.B."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Emery S.B."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Lesperance M.M."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Lesperance M.M."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Boerst A.K."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Boerst A.K."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Kim T.B."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/author"Kim T.B."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/name"Arch. Otolaryngol. Head Neck Surg."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/name"Arch. Otolaryngol. Head Neck Surg."xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/pages"54-59"xsd:string
http://purl.uniprot.org/citations/21242547http://purl.uniprot.org/core/pages"54-59"xsd:string
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