Abstract
BackgroundIn 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.MethodsOne 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.ResultsThe 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.ConclusionIn 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.
Highlights
As one of the most common sensory disorders worldwide, hearing loss (HL) is a heterogeneous group of disorders in which both genetic and environmental risk factors are contributing to the disease etiology (Hashemzadeh, Farhud, & Patton, 2007)
The mutation c.35delG was the most prevalent pathogenic variant with 61.9% allele frequency, of which 57.1% of the mutant alleles were in homozygous state and 4.8% were compound heterozygous (Table 1)
Our study showed that the c.35delG mutation was found in 9.92% of 131 unrelated cases of autosomal recessive non‐syndromic hearing loss (ARNSHL), either sporadic or familial
Summary
As one of the most common sensory disorders worldwide, hearing loss (HL) is a heterogeneous group of disorders in which both genetic and environmental risk factors are contributing to the disease etiology (Hashemzadeh, Farhud, & Patton, 2007). At least 50% of prelingual hearing loss in industrialized countries has been referred to genetic causes (Marres, 1998). 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. Results: The GJB2 variants were found in 16.79% (22/131) of the patients. Allele frequency of the c.35delG as the pathogenic variant was the most common with 59.52% (25/42). 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
