Prevalence of DFNB1 mutations in Slovak patients with non-syndromic hearing loss.

Objective: Non-syndromic hearing loss is one of the most common genetically determined diseases in human. The incidence is approximately 1:700 and most of the cases are caused by mutations in specific locus - DFNB1, which contains two genes -GJB2 and GJB6. For the GJB2 gene following mutations are most prevalent in specific populations - 35delG, 235delC, W24X and 167delT for Caucasians, Asians, Indians and Ashkenazi Jews, respectively. Large deletions are common in GJB6 gene. Many other mutations and polymorphisms were found in DFNB1 focused non-syndromic hearing loss studies thus the establishment of optimal screening protocol should be based on population specific mutation screening studies and is an objective in our study.

Methods: In our study samples from 273 non-syndromic hearing loss patients were screened for mutations in coding and non-coding part of GJB2 gene and large deletion in GJB6 gene - del(GJB6-D13S1830).

Results: Causal mutation on both chromosomes was detected in 24.57% of patients, another 9.9% carried causal mutation on one chromosome. Totally 7 polymorphisms: V27I, M34T, F83L, 354 C→T, R127H, V153I, 684 C→A and 11 causal mutations: IVS1+1 G→A, 35delG, W24X, V37I, E47X, 167delT, V84M, L90P, 310del14, 333-334delAA, R184Q were detected. No patient carried the GJB6 deletion mutation (del(GJB6-D13S1830)).

Conclusions: According to our results sequencing of GJB2 coding regions and IVS1+1G→A specific detection should explain approximately 25% of sporadic NSHL cases and these two tests are relevant for use as routine screening protocol for NSHL in Slovakia. The GJB6 del(GJB6-D13S1830) mutation was not detected in any of NSHL samples therefore it is not necessary to implement it in our routine screening protocol.