Frequency of c.35delG Mutation in GJB2 gene in Patients with Autosomal Recessive Non-Syndromic Hearing Loss of Five Ethnic Groups in Golestan, Iran

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. DFNB1 locus containing gap junction beta-2 protein (GJB2) 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.35delG mutation among families with different ethnicities residing in Golestan province of Iran.

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.

In our study, 28 out of 128 families with ARNSHL had c.35delG mutation. We observed that 15.4% of subjects had c.35delG+/c.35delG+ genotype, 7.4% had c.35delG+/normal genotype and 77.2% had no c.35delG mutation. The overall allele frequency of c.35delG is 19.1%. Regarding the consanguineous marriage rate, the Sistani ethnic group showed the highest (91%), and Azeris had the lowest rates (55%).

The present work showed that severe forms of ARNSHL are associated with c.35delG homozygous mutation in comparison to other genotypes. We also demonstrated that c.35delG mutation is more prevalent in Turkmen and Fars ethnic groups in Golestan province of Iran.