High frequency hearing loss correlated with mutations in the GJB2 gene

Abstract

Genetic hearing impairment affects approximately 1/2000 live births. Mutations in one gene, GJB2, coding for connexin 26 cause 10%-20% of all genetic sensorineural hearing loss. Mutation analysis in the GJB2 gene and audiology were performed on 106 families presenting with at least one child with congenital hearing loss. The families were recruited from a hospital-based multidisciplinary clinic, which functions to investigate the aetiology of sensorineural hearing loss in children and which serves an ethnically diverse population. In 74 families (80 children), the aetiology was consistent with non-syndromic recessive hearing loss. Six different connexin 26 mutations, including one novel mutation, were identified. We show that GJB2 mutations cause a range of phenotypes from mild to profound hearing impairment and that loss of hearing in the high frequency range (4000-8000 Hz) is a characteristic feature in children with molecularly diagnosed connexin 26 hearing impairment. We also demonstrate that this type of audiology and high frequency hearing loss is found in a similar-sized group of deaf children in whom a mutation could only be found in one of the connexin 26 alleles, suggesting connexin 26 involvement in the aetiology of hearing loss in these cases. In our study of the M34T mutation, only compound heterozygotes exhibited hearing loss, suggesting autosomal recessive inheritance.

Correlação entre dados audiométricos e mutação 35delG em dez pacientes

“…A prevalence of 3% was also assessed for each one of the mutations V37I and Delta (GJB6-D13S1830), found in the study. These results are concordant with previous studies reported in the literature, conducted in several populations [22][23][24][25][26] . The relative contribution of the 35delG mutation to the non-syndromic hearing loss in these populations varied from 0% (Oman, Korea, Japan) to 70% (Italy, Spain, Greece), demonstrating the genetic heterogeneity among the different countries, even though some of these …”

“…studies were based on a small number of patients, besides the differences in the impairment investigation criteria and the mutation screening methods 23,[27][28][29][30] . Recent studies found a 342 thousand base-pair (342 Kb) deletion close to the GJB6 [D(GJB6 -D13S1830)] gene, suggesting that this mutation could cause non-syndromic recessive hearing loss, either by a homozygous deletion or by digenic penetrance of the deletion in the GJB6 gene, associated with a trans mutation in the GJB2 gene in the heterozygous cases 24 .…”

Methodology of a multistate study of congenital hearing loss: Preliminary data from Utah newborn screening

“…Mutation detection for GJB2 (connexin 26) is accomplished by direct sequencing as described by Wilcox et al [2000] and Denoyelle et al [1999]. The amplification of the full-length 681-bp coding sequences and flanking acceptor splicing site of the GJB2 (connexin 26) was carried out by three polymerase chain reactions (PCRs).…”

Detection of Connexion 26 GENE (GJB2) Mutations in Cases of Congenital Non Syndromic Deafness

“…The six putatively causative variants (Table 3). Three mutations, c.35delG, c.167delT, and c.235delC, are found to be the most frequent mutations in Caucasian, Ashkenazi Jewish, and Asian populations, respectively (Gabriel et al [18], Morell et al [19], Ohtsuka et al [20], Park et al [21], Rabionet et al [4], Wilcox et al [22], Abe et al [24], Ballana et al [25], Roux et al [26]). In an Iranian study by Galehdari et al [23] it was reported an absence of any mutation associated with deafness, including the commonly described mutations 35delG, 427C [ T(R143 W), 167delT, and 235delC in the connexin-26 (GJB2) gene in an ethnic group of the Iranian Arab NSARD patients.…”

“…GJB2 formed by Connexin 26 gene is used for returning potassium ions to the endolymph, which plays a role in sensorineural hearing functions [4]. Mutations in the GJB2 gene are responsible for 50 % of all cases of childhood prelingual ARNSHL the most common of which is 35delG, also referred to as 30delG [4][5][6][7]. It has been determined that more than 50 % of autosomal recessive non-syndromic hearing impairments result from the 35delG mutation in Northern and Southern European and American Caucasian populations [5].…”