Dataset Information

GJB2 mutations and degree of hearing loss: a multicenter study.

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.

SUBMITTER: Snoeckx RL

PROVIDER: S-EPMC1285178 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature

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GJB2 mutations and degree of hearing loss: a multicenter study.

Snoeckx Rikkert L RL Huygen Patrick L M PL Feldmann Delphine D Marlin Sandrine S Denoyelle Françoise F Waligora Jaroslaw J Mueller-Malesinska Malgorzata M Pollak Agneszka A Ploski Rafal R Murgia Alessandra A Orzan Eva E Castorina Pierangela P Ambrosetti Umberto U Nowakowska-Szyrwinska Ewa E Bal Jerzy J Wiszniewski Wojciech W Janecke Andreas R AR Nekahm-Heis Doris D Seeman Pavel P Bendova Olga O Kenna Margaret A MA Frangulov Anna A Rehm Heidi L HL Tekin Mustafa M Incesulu Armagan A Dahl Hans-Henrik M HH du Sart Desirée D Jenkins Lucy L Lucas Deirdre D Bitner-Glindzicz Maria M Avraham Karen B KB Brownstein Zippora Z del Castillo Ignacio I Moreno Felipe F Blin Nikolaus N Pfister Markus M Sziklai Istvan I Toth Timea T Kelley Philip M PM Cohn Edward S ES Van Maldergem Lionel L Hilbert Pascale P Roux Anne-Françoise AF Mondain Michel M Hoefsloot Lies H LH Cremers Cor W R J CW Löppönen Tuija T Löppönen Heikki H Parving Agnete A Gronskov Karen K Schrijver Iris I Roberson Joseph J Gualandi Francesca F Martini Alessandro A Lina-Granade Geneviéve G Pallares-Ruiz Nathalie N Correia Céu C Fialho Graça G Cryns Kim K Hilgert Nele N Van de Heyning Paul P Nishimura Carla J CJ Smith Richard J H RJ Van Camp Guy G

American journal of human genetics 20051019 6

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 assess ...[more]

PMID: 16380907

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Project description:BackgroundHearing loss is caused by several environmental and genetic factors and the proportion attributed to inherited causes is assumed at 50?~?60% . Mutations in GJB2 and mitochondrial DNA (mtDNA) 12S rRNA are the most common molecular etiology for nonsyndromic sensorineural hearing loss (NSHL). The mutation spectra of these genes vary among different ethnic groups.MethodsTo add the molecular etiologic information of hearing loss in the Chinese population, a total of 658 unrelated patients with NSHL from Jiangsu Province of China were selected for mutational screening including GJB2 and mtDNA 12S rRNA genes using PCR and DNA sequencing technology. As for controls, 462 normal-hearing individuals were collected.ResultsA total of 9 pathogenic mutations in the GJB2 and 7 pathogenic mutations in the 12S rRNA gene were identified. Of all patients, 70 had monoallelic GJB2 coding region mutation in the heterozygous state, 94 carried two confirmed pathogenic mutations including 79 homozygotes and 15 compound heterozygotes. The 235delC appears to be the most common deafness-causing GJB2 mutation (102/658, 15.50% ). No mutations or variants in the GJB2 exon1 and basal promoter region were found. In these patients, 4 subjects carried the m.1494C?>?T mutation (0.61% ) and 39 subjects harbored the m.1555A?>?G mutation (5.93% ) in mtDNA 12S rRNA gene. A novel sequence variant at m.1222A?>?G in the 12S rRNA gene was identified, which could alter the secondary structure of the 12S rRNA.ConclusionThe mutation spectrum and prevalence of GJB2 and mtDNA 12S rRNA genes in Jiangsu population are similar to other areas of China. There are in total 31.46% of the patients with NSHL carry deafness-causing mutation in GJB2 or mtDNA 12S rRNA genes. Mutation in GJB2 gene is the most common factor, mtDNA 12S rRNA also plays an important part in the pathogenesis of hearing loss in Jiangsu Province areas. The m.1222A?>?G was found to be a new candidate mutation associated with hearing loss. Our results indicated the necessity of genetic screening for mutations of these genes in Jiangsu patients with NSHL.

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GJB2 mutations and degree of hearing loss: a multicenter study.

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GJB2 mutations and degree of hearing loss: a multicenter study.

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