Molecular genetic examination of Czech patients and families with hereditary hearing loss and with excluded mutations in GJB2 gene

Hearing loss is the most common sensory deficit and it affects 1 of 300 newborns. Genetic causes are responsible for 50-75% of cases. The most common cause of hereditary hearing loss (HHL) are mutations of GJB2 gene, which account for 43 % of non-syndromic hearing loss (NSHL) in the Czech Republic. According to literature, the second most common genetic cause of HHL are mutations in SLC26A4 gene. Bialelic mutations in this gene cause NSHL of type 4 (DFNB4) and Pendred syndrome (PS), which means a hearing loss associated with thyroid impairment. A typical symptom of both units is Enlarged Vestibular Aqueduct (EVA) and Mondini dysplasia (MD) on the HRCT of temporal bone. Sequencing of SLC26A4 gene was used to examine 315 patients with NSHL where bialelic mutations in GJB2 gene were dismissed, out of that 30 familiar and 285 sporadic cases. At least one pathogenic mutation in SLC26A4 gene was found in 6.9% patients and bialelic pathogenic mutations in 2.6% patients, however for familial cases it was 14.8% patients with at least one mutation, or 7.4% patients with both identified mutations. In the group of cochlear implant users with no GJB2 mutations at least one pathogenic mutation was found in 13.0% and bialelic mutation in 7.6%. The SLC26A4 mutations appear to represent the second most common cause..