Forty-six genes causing nonsyndromic hearing impairment: Which ones should be analyzed in DNA diagnostics?

Nele Hilgert; Richard J.H Smith; Guy Van Camp

doi:10.1016/j.mrrev.2008.08.002

Back

Forty-six genes causing nonsyndromic hearing impairment: Which ones should be analyzed in DNA diagnostics?

Journal article

Open access

Peer reviewed

Forty-six genes causing nonsyndromic hearing impairment: Which ones should be analyzed in DNA diagnostics?

Nele Hilgert, Richard J.H Smith and Guy Van Camp

Mutation research. Reviews in mutation research, Vol.681(2), pp.189-196

2009

DOI: 10.1016/j.mrrev.2008.08.002

PMCID: PMC2847850

PMID: 18804553

Files and links (1)

url

http://doi.org/10.1016/j.mrrev.2008.08.002View

Open Access

Abstract

Hearing impairment is the most common sensory disorder, present in 1 of every 500 newborns. With 46 genes implicated in nonsyndromic hearing loss, it is also an extremely heterogeneous trait. Here, we categorize for the first time all mutations reported in nonsyndromic deafness genes, both worldwide and more specifically in Caucasians. The most frequent genes implicated in autosomal recessive nonsyndromic hearing loss are GJB2, which is responsible for more than half of cases, followed by SLC26A4, MYO15A, OTOF, CDH23 and TMC1. None of the genes associated with autosomal dominant nonsyndromic hearing loss accounts for a preponderance of cases, although mutations are somewhat more frequently reported in WFS1, KCNQ4, COCH and GJB2. Only a minority of these genes is currently included in genetic diagnostics, the selection criteria typically reflecting: (1) high frequency as a cause of deafness (i.e. GJB2); (2) association with another recognisable feature (i.e. SLC26A4 and enlarged vestibular aqueduct); or (3) a recognisable audioprofile (i.e. WFS1). New and powerful DNA sequencing technologies have been developed over the past few years, but have not yet found their way into DNA diagnostics. Implementing these technologies is likely to happen within the next 5 years, and will cause a breakthrough in terms of power and cost efficiency. It will become possible to analyze most – if not all – deafness genes, as opposed to one or a few genes currently. This ability will greatly improve DNA diagnostics, provide epidemiological data on gene-based mutation frequencies, and reveal novel genotype–phenotype correlations.

Gene frequencies

ADNSHL

ARNSHL

GJB2

Hereditary hearing loss

Genetic counselling

Details

Title: Subtitle: Forty-six genes causing nonsyndromic hearing impairment: Which ones should be analyzed in DNA diagnostics?
Creators: Nele Hilgert - Department of Medical Genetics, University of Antwerp (UA), Universiteitsplein 1, B-2610 Antwerp, Belgium
Richard J.H Smith - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa city, IA 52242, USA
Guy Van Camp - Department of Medical Genetics, University of Antwerp (UA), Universiteitsplein 1, B-2610 Antwerp, Belgium
Resource Type: Journal article
Publication Details: Mutation research. Reviews in mutation research, Vol.681(2), pp.189-196
DOI: 10.1016/j.mrrev.2008.08.002
PMID: 18804553
PMCID: PMC2847850
NLM abbreviation: Mutat Res Rev Mutat Res
ISSN: 1383-5742
eISSN: 1388-2139
Publisher: Elsevier B.V
Language: English
Date published: 2009
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984007188402771

Metrics

21 Record Views

378 Times Cited - Web of Science

See more details