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Background: In the present study, we investigate the prevalence of the GJB2 gene mutations, and deletions in the GJB6 gene, namely del (GJB6‐D13S1830) and del (GJB6‐D13S1854), in patients with autosomal recessive non‐syndromic hearing loss (ARNSHL) from the central region of Iran. Methods: One hundred and thirty‐one unrelated ARNSHL cases from the central part of Iran were recruited. Among them, 81% (106 cases) had at least two affected relatives. Coding and noncoding regions of the GJB2 gene were sequenced. Multiplex PCR was used for analysis of del (GJB6‐D13S1830) and del (GJB6‐D13S1854) deletions in GJB6. Results: The GJB2 variants were found in 16.79% (22/131) of the patients. The pathogenic variants were 21/131 (16.03%). The nonpathogenic variants were 1/131 (0. 07%). Allele frequency of the c.35delG as the pathogenic variant was the most common with 59.52% (25/42). The remaining pathogenic variants were c.235delC, p.T8M, p.R32H, p.R143Q, p.R143W, c‐23+1G>A. The only nonpathogenic variant was polymorphism p.V27I. Further segregation analysis showed that variant of p.R143Q might have incomplete penetrance. None of the patients had targeted deletions in the GJB6 gene. Conclusion: In comparison with reports from other areas of Iran, c.35delG demonstrates the highest frequency within the central region (accounting for 57.14% of cases), probably resulting from the founder effect and consanguineous marriage. The pathology of ARNSHL in such patients could be attributed to defects in Connexin 26 encoded by GJB2. [ABSTRACT FROM AUTHOR]

Objective: To identify the spectrum of mutations in connexin 26 gene and frequency of two deletions in connexin 30 gene in central Iran., Methods: After extraction of DNA from 300 blood samples, connexin 26 gene coding region was amplified using specific primers. PCR products were used for bidirectional sequencing. Multiplex PCR was used for detection of del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene., Results: Eighteen different mutations including two novel variants in GJB2 gene were detected. The GJB2 mutations were observed in 23.3% of all the subjects. In addition, none of the deaf patients carried the del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene. The 35delG mutation was the most common mutation, accounting for 32.65% of the mutant alleles., Conclusion: The present study indicates that mutations in the GJB2 gene particularly 35delG are important causes for ARNSHL. 60% of the patients were heterozygous carriers. Thus, further investigation is needed to detect the genetic cause of hearing loss in patients with mono allelic mutations in the coding region of GJB2., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Hearing loss is a serious sensory defect in the world. Mutations in the GJB2 and GJB6 genes are the major causes of autosomal recessive nonsyndromic hearing loss (NSHL). Recently, three major large deletions in the GJB6 gene including del(GJB6-D13S1830), del(GJB6-D13S1854), and a > 920 kb deletion have been reported to form double heterozygosity with GJB2. This may suggest that deletions involving GJB6 may be responsible for some NSHL., Methods: We designed a real time SYBR green-based PCR to quantify a common deleted region in GJB6 gene. The amplified region covers the area which has been seen to be deleted in all of the above reports. We selected nine families heterozygous for different mutations in GJB2 gene to investigate the presence of deletions in the GJB6 gene. The samples were run along with controls for normal hearing and heterozygous and homozygous for GJB2 mutations to optimize our method. As a reference gene or external standard, a segment of the CLCN7 gene was also quantified as well., Results: We did not detect any deletion in the GJB6 gene., Conclusions: Using this method, any deletion involving GJB6 gene can be detected in a rapid and sensitive way.

Objective: DFNB1 locus has been reported as a major cause of autosomal recessive non-syndromic hearing loss (ARNSHL) worldwide. 35delG and del(GJB6-D13S1830) are thought to be two common mutations in this locus among Caucasians. The aim of this study is to determine the significance of these two mutations in aetiology of ARNSHL in Iran., Methods: One hundred and thirty-three unrelated patients with ARNSHL were tested by using multiplex allele-specific PCR assay after validation by positive control samples., Results: The frequency of 35delG was about 18.5%, however, del(GJB6-D13S1830) was not found in the studied patients. Parental consanguinity was observed in 50% of 35delG-mutated families., Conclusions: Our results support founder effect regarding these mutations.