Prevalence of variants in DFNB1 locus in Serbian patients with autosomal recessive non-syndromic hearing loss

Abstract

Hearing impairment is the most common sensorineural disorder in humans and many genes have been identified as causable. Despite genetic heterogeneity, a single locus, DFNB1, that contains genes GJB2 and GJB6, accounts for up to 50% of all cases. Aim of this study was to determine prevalence of identified variants in DFNB1 locus in patients from Serbia with autosomal recessive non-syndromic hearing loss (ARNSHL). In this study, PCR-ARMS and direct sequencing of the GJB2 and GJB6 genes was carried out in 54 probands and relatives from Serbia with nonsyndromic hearing loss (NSHL). In 31 patients a series of variants have been identified in the GJB2 gene. Fully characterized genotype with bi-allelic mutations was observed in 40.74% of the probands (22/54). The remaining probands were either identified in the heterozygote form (9/54) or were identified with no (23/54) causing variants for the tested genes. A total of seven different mutations were found with following allele frequencies: c.35delG (31.48%), c.71G>A (6.48%), c.313_326del (5.56%), c.101T>C (1.85%), c.380G>A (1.85%), c.79G>A (0.92%) and c.269T>C (0.92%). The molecular basis of NSHL in patients from Serbia was analyzed for the first time in this study. The results have important implication to the development of the genetic diagnosis of deafness, genetic counseling, and early treatment in our country. Also, our findings contribute to the knowledge of geographic distribution of DFNB1 mutations.