Journal article
GJB2 mutations and degree of hearing loss: a multicenter study
American journal of human genetics, Vol.77(6), pp.945-957
12/2005
DOI: 10.1086/497996
PMCID: PMC1285178
PMID: 16380907
Abstract
Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes.
Details
- Title: Subtitle
- GJB2 mutations and degree of hearing loss: a multicenter study
- Creators
- Rikkert L Snoeckx - Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, BelgiumPatrick L M HuygenDelphine FeldmannFrançoise DenoyelleSandrine MarlinJaroslaw WaligoraMalgorzata Mueller-MalesinskaAgneszka PollakRafal PloskiAlessandra MurgiaEva OrzanPierangela CastorinaUmberto AmbrosettiEwa Nowakowska-SzyrwinskaJerzy BalWojciech WiszniewskiAndreas R JaneckeDoris Nekahm-HeisPavel SeemanOlga BendovaMargaret A KennaAnna FrangulovHeidi L RehmMustafa TekinArmagan IncesuluHans-Henrik M DahlDesirée du SartLucy JenkinsDeirdre LucasMaria Bitner-GlindziczKaren B AvrahamZippora BrownsteinIgnacio del CastilloFelipe MorenoNikolaus BlinMarkus PfisterIstvan SziklaiTimea TothPhilip M KelleyEdward S CohnLionel Van MaldergemPascale HilbertAnne-Françoise RouxMichel MondainLies H HoefslootCor W R J CremersTuija LöppönenHeikki LöppönenAgnete ParvingKaren GronskovIris SchrijverJoseph RobersonFrancesca GualandiAlessandro MartiniGeneviéve Lina-GranadeNathalie Pallares-RuizCéu CorreiaGraça FialhoKim CrynsNele HilgertPaul Van de HeyningCarla J NishimuraRichard J H SmithGuy Van Camp
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.77(6), pp.945-957
- DOI
- 10.1086/497996
- PMID
- 16380907
- PMCID
- PMC1285178
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- United States
- Grant note
- DC005248 / NIDCD NIH HHS R01 DC005248 / NIDCD NIH HHS R01-DC02842 / NIDCD NIH HHS R01 DC002842 / NIDCD NIH HHS
- Language
- English
- Date published
- 12/2005
- 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
- 9984006427502771
Metrics
35 Record Views