Screening for GJB2 and GJB6 mutations in the Slovak deaf population

Abstract

Introduction: Mutations of connexin genes account for up to 50% of prelingual bilateral sensorineural hearing loss (SNHL). In Slovakia the deaf population is estimated to reach about 9000 individuals. However, reliable data on bilateral SNHL etiology in Slovakia are not available to date. The aim of presented study was to analyze the GJB2 and GJB6 genes and describe their mutation spectrum in patients with bilateral SNHL and thus to determine epidemiology of one of the most dominant causes of SNHL in Slovakia. Methods: Since 2010 we performed molecular-genetic testing for GJB2 and GJB6 mutations in >500 subjects suffering from bilateral SNHL, that included 375 unrelated individuals selected for epidemiology analyses. Patients were recruited at 2 ORL clinics in Bratislava and special schools for hearing impaired children throughout Slovakia. Inclusion criteria were bilateral SNHL and age below 60 years at the time of hearing loss diagnosis. Direct sequencing and MLPA was used for DNA analysis. Results: We identified 11 mutations and six polymorphisms in GJB2 gene. Homozygous mutations occurred in 22% and compound heterozygotes in 9% of subjects. Negative subjects, without any pathogenic allele found accounted for 61%. Mutations c.35delG and c.71G>A were recorded most frequently (60.4% and 15.8% respectively). The large GJB6 deletion (delD13S1830) was found in 1 family.Conclusions: DNA analysis of patients with SNHL revealed mutation spectrum of GJB2 and GJB6 genes in our cohort and also confirmed exact genetic cause of hearing loss in almost one third of investigated subjects. Our results represent fundamental data for genetic counseling, clinical prognosis, improvement of diagnostic tools for clinical practice and possible personalized treatment in future.Supported by: Grants APVV 0148-10 and VEGA 1/0465/11Der Erstautor gibt keinen Interessenkonflikt an