Frequency of c.۳۵delG Mutation in GJB۲ gene in Patients with Autosomal Recessive Non-Syndromic Hearing Loss of Five Ethnic Groups in Golestan, Iran

Background: Hereditary Hearing Loss (HL) is one of the most prevalent sensorineural disorders worldwide. Several hundreds of genes have been reported to have associations with this condition. Autosomal Recessive Non-Syndromic Hearing Loss (ARNSHL), with the highest frequency of severe to profound types of deafness, is responsible for the majority of non-syndromic HL. DFNB۱ locus containing gap junction beta-۲ protein (GJB۲) gene is the main reported pathogenic variant in most cases of non-syndromic deafness globally. In the present study, we investigated the allele frequency of c.۳۵delG mutation among families with different ethnicities residing in Golestan province of Iran.Methods: Audiological assessments, including pure-tone audiometry (PTA), tympanometry, and otoacoustic emission (OAE) tests, have been conducted to include and group subjects. Blood samples have been taken from probands and all their family members; and they have undergone allele-specific polymerase chain reaction (ASPCR) test. Moreover, direct sequencing has been performed to confirm the PCR results.Results: In our study, ۲۸ out of ۱۲۸ families with ARNSHL had c.۳۵delG mutation. We observed that ۱۵.۴% of subjects had c.۳۵delG+/c.۳۵delG+ genotype, ۷.۴% had c.۳۵delG+/normal genotype and ۷۷.۲% had no c.۳۵delG mutation. The overall allele frequency of c.۳۵delG is ۱۹.۱%. Regarding the consanguineous marriage rate, the Sistani ethnic group showed the highest (۹۱%), and Azeris had the lowest rates (۵۵%).Conclusion: The present work showed that severe forms of ARNSHL are associated with c.۳۵delG homozygous mutation in comparison to other genotypes. We also demonstrated that c.۳۵delG mutation is more prevalent in Turkmen and Fars ethnic groups in Golestan province of Iran.

Keywords:

Hearing Loss , , , , , C.۳۵delG Mutation , , , , , GJB۲ gene , , , , , Connexin ۲۶ , , , , , autosomal recessive nonsyndromic hearing loss (ARNSHL)