Genetic analysis in patients with nonsyndromic hearing loss

Purpose: In this study, our main aim has been to determine those patients with familial non-syndromic sensorineural hearing loss, to identify the prevalence distribution of genetic data known in regard to our region through these patients' genetic analyses, to establish the association between their phenotype and genotype and to find new genes. Material and Method Patients who were diagnosed with familial non syndromic sensorineural hearing loss, and who applied to the Polyclinic of Otorhinolaryngologic diseases, Dicle University, between 2013 and 2016, were included into the study. The patients' detailed anamnesis, examinations performed and their hearing threshold tests were recorded. The families' pedigrees were drawn and included in the review. Blood samples of the patients and of at least 2 family members were taken and reviewed under appropriate conditions by the department of Child Genetic Science, Ankara University. Connexin 26 (GJB2), identified by the DNA gene sequencing method, and the mitochondrial gene mutations by the cutting with enzyme method were scanned. The DNA samples of patients, whose Connexin 26 and mitochondrial gene mutations were not identified, were scanned at Miami University, John P. Hussman Institute of Human Genomics laboratory for other gene mutations, known to cause the other non-syndromic hearing losses, by using the whole exome sequencing method, which is one of the new generation sequencing methods. As to the samples, in whom hearing loss could not be explained after scanning for other gene mutations known to cause hearing loss, the families' genetic mappings were drawn, and new gene mutations were researched. Findings Our study was carried out on 57 families with familial nonsyndromic hearing loss. From among these families, 244 individuals were assessed. Familial nonsyndromic hearing loss was determined in 92 of those individuals. Our genetic analyses were performed on one proband patient chosen from each family. As a result of our study, genetic mutations were determined to be the main reason for hearing loss in 23 families (40%). There existed third degree consanguineous marriage in 82,6% and severe-to-profound hearing loss in 91,3% of those patients who were determined to have genetic mutations. Gene mutations were determined as follows: Connexin 26 (GJB2) (%12.2) in 7 patients; TMIE (%7.01) in 4; MYO15A (%5.2) in 3; SLC26A4 (%3.5) in 2; ESRRB (%3.5) in 2; TMPRSS3 (%3.5) in 2; GIPC3 (%1.7) in 1; MYO6 (%1.7) in 1; MYO7A (%1.7) in 1. Result In our study, Connexin 26 mutations were determined to be the most frequent reason for hearing loss. As the most common reason for Connexin 26 mutations, c.35delG was identified. The prevalence of genetic mutations leading to familial non-syndromic hearing loss was also determined for our region, During our study, we were not able to identify new gene mutations, however.