Abstract
BackgroundMutations in the GJB2 gene are the most common cause of nonsyndromic recessive hearing loss in China. In about 6% of Chinese patients with severe to profound sensorineural hearing impairment, only monoallelic GJB2 mutations known to be either recessive or of unclear pathogenicity have been identified. This paper reports the prevalence of the GJB2 IVS1+1G>A mutation in a population of Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2.MethodsTwo hundred and twelve patients, screened from 7133 cases of nonsyndromic hearing loss in China, with monoallelic mutation (mainly frameshift and nonsense mutation) in the coding region of GJB2 were examined for the GJB2 IVS1+1G>A mutation and mutations in the promoter region of this gene. Two hundred and sixty-two nonsyndromic hearing loss patients without GJB2 mutation and 105 controls with normal hearing were also tested for the GJB2 IVS1+1G>A mutation by sequencing.ResultsFour patients with monoallelic mutation in the coding region of GJB2 were found carrying the GJB2 IVS1+1G>A mutation on the opposite allele. One patient with the GJB2 c.235delC mutation carried one variant, -3175 C>T, in exon 1 of GJB2. Neither GJB2 IVS1+1G>A mutation nor any variant in exon 1 of GJB2 was found in the 262 nonsyndromic hearing loss patients without GJB2 mutation or in the 105 normal hearing controls.ConclusionTesting for the GJB2 IVS 1+1 G to A mutation explained deafness in 1.89% of Chinese GJB2 monoallelic patients, and it should be included in routine testing of patients with GJB2 monoallelic pathogenic mutation.
Highlights
Hereditary hearing loss is a genetically heterogeneous disorder in humans, with an incidence rate of approximately 1 in 1000 children [1]
More than 150 mutations, polymorphisms, and unclassified variants have been described in the GJB2 gene, which account for the molecular etiology of 10-50% of patients with nonsyndromic hearing impairment http://davinci.crg.es/deafness
The results of GJB2 screening performed to date have indicated that a substantial fraction of patients (6-15%) carry only one pathogenic mutation in the GJB2 gene with either recessive or unclear pathogenicity, despite direct sequencing of the entire coding region of the gene [12,13,14]
Summary
Hereditary hearing loss is a genetically heterogeneous disorder in humans, with an incidence rate of approximately 1 in 1000 children [1]. We tested Chinese patients with only one monoallelic mutation in the coding region of GJB2 for the presence of this mutation, but the results indicated this to be a very rare cause of hearing loss in the Chinese population, and this is not a major additional factor in our monoallelic patients (unpublished). This study focused on clarifying the impact of GJB2 IVS1+1G>A mutation and the promoter region of this gene among Chinese patients with hearing loss, especially those with pathogenic mutation in only one allele of the GJB2 gene coding region. This paper reports the prevalence of the GJB2 IVS1+1G>A mutation in a population of Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2
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