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GJB2 c.−23+1G>A mutation is second most common mutation among Iranian individuals with autosomal recessive hearing loss

  • Otology
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Abstract

GJB2 mutation analysis is used routinely as a first step in genetic testing for autosomal recessive non-syndromic sensorineural hearing loss. Although most GJB2 mutations can be detected by sequencing of the exon 2 of this gene, a prevalent splice mutation, c.−23+1G>A (IVS1+1G>A), is not usually included in the analyzed region. In this study, we have developed an ARMS-PCR strategy for detection of this mutation among Iranian deaf individuals. A total of 418 Iranian individuals with hearing loss consistent with autosomal recessive non-syndromic sensorineural hearing loss based on audiological test result, medical history, physical examination and pedigree of the family, were included in this study. c.35delG and c.−23+1G>A mutations were detected by using ARMS-PCR. Direct sequencing of the exon 2 of the GJB2 gene was performed for mutation analysis of the coding region of this gene. Among 418 investigated cases, a total of 81 patients (~19.4 %) with biallelic pathogenic mutations in the GJB2 gene and 13 cases with only one pathogenic mutant allele were identified. The total allele frequencies of the two most frequent mutations, c.35delG and c.−23+1G>A, among mutated alleles were found to be around 59 and 15.7 %, respectively. High frequency of the c.35delG and c.−23+1G>A mutations among Iranian deaf individuals shows the importance of developing rapid and cost-effective methods for primary mutation screening methods before performing direct sequencing.

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Acknowledgments

This study was supported by the Kawsar Human Genetics Research Center and Pasteur Institute of Iran. The authors would like to gratefully thank the patients and their families who took the time to contribute to this study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Pasteur St., Tehran, Iran

    Sirous Zeinali & Elham Davoudi-Dehaghani

  2. Medical Genetics Lab, Kawsar Human Genetics Research Center, No. 41 Majlesi St., Vali Asr St., 1595645513, Tehran, Iran

    Sirous Zeinali, Sarah Azadmehr, Samira DabbaghBagheri, Hamideh Bagherian, Mojdeh Jamali, Fatemeh Zafarghandimotlagh, Mahboobeh Masoodifard, Ameneh BandehiSarhaddi, Leili Rejali & Sepideh Sahebi

  3. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Elham Davoudi-Dehaghani

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  1. Sirous Zeinali
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Correspondence to Sirous Zeinali.

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Zeinali, S., Davoudi-Dehaghani, E., Azadmehr, S. et al. GJB2 c.−23+1G>A mutation is second most common mutation among Iranian individuals with autosomal recessive hearing loss. Eur Arch Otorhinolaryngol 272, 2255–2259 (2015). https://doi.org/10.1007/s00405-014-3171-7

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