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Arch Otolaryngol Head Neck Surg. 2011 Jan;137(1):54-9. doi: 10.1001/archoto.2010.234.

Autosomal dominant progressive sensorineural hearing loss due to a novel mutation in the KCNQ4 gene.

Author information

1
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, 48109-5241, USA.

Erratum in

  • Arch Otolaryngol Head Neck Surg. 2011 Jul;137(7):711.

Abstract

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.

PMID:
21242547
PMCID:
PMC3278911
DOI:
10.1001/archoto.2010.234
[Indexed for MEDLINE]
Free PMC Article

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