Audiological features in Serbian patients with hearing impairment identified with c.35delG in the GJB2 gene

Introduction/Objective. Hearing impairment (HI) is the most common sensorineural disorder with an incidence of 1/700-1000 newborns. Variants in the GJB2 gene are the major cause of autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL). The degree of HI in patients with detected mutations in GJB2 gene ranges from mild to profound. The aim of this study was to determine possible genotype-phenotype association between audiometric characteristics and detected genotypes in ARNSHL patients from Serbia. Methods. Ninety-two patients with ARNSHL underwent genetic analysis with PCR-ARMS and sequencing of the GJB2 gene. Audiological analyses were obtained in all patients using a combination of several methods to estimate the degree of hearing loss. Results. Audiological analysis performed in the 92 probands showed moderate to profound range of hearing loss. All identified pathogenic variants accounted for 42.39% of the mutant alleles (78/184 alleles), with the c.35delG mutation being the most frequent (30.43%). Genotype-phenotype correlation in an isolated group of 37 patients bearing c.35delG in the homozygous, compound heterozygous or heterozygous state. In this group the majority of patients (30/37, 81.08%) exhibited severe to profound hearing deficit. Conclusion. Association between genotype and the degree of hearing impairment in patients analyzed in this study demonstrated that patients with bi-allelic truncating mutations i.e. c.35delG, associate with the more severe hearing loss when compared with those identified with only one affected allele. The various degrees of hearing impairment observed in heterozygous patients could be explained by the presence of an undetected second mutation or other modifier genes or environmental causes.