Classification and genetic analysis in patients with inner ear anomalies

Aim In this study, it was aimed to evaluate and classify the patients who admitted to our clinic with sensorineural hearing loss and who had an inner ear anomaly by imaging methods and to determine the genetic mutation analysis of these patients. Materials and Methods We studied patients who presented to the Dicle University Otorhinolaryngology Outpatient Clinic with hearing loss between 2016 and 2019 and were diagnosed internal ear anomalies with temporal computerized tomography (CT) and magnetic resonance (MR). Detailed anamnesis, examination, hearing thresholds, findings ct and mr of the patients were recorded. By taking blood samples of the patients, all result were examined by Ankara University Pediatric Genetics Department under appropriate conditions. Konneksin 26 (GJB2) and mitochondrial gene mutations were screened by DNA sequencing. 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 and gene mutations that may be associated with inner ear anomalies, by using the whole exome sequencing method, which is one of the new generation sequencing methods Results Our study was performed on 22 patients with an inner ear anomaly. In our study, 44 ears were evaluated in 22 patients. Internal ear malformations were observed in 40 ears. While 18 patients had inner ear malformations in both ears, 4 patients had inner ear information in one ear. Two of the four ears were the right ear and the other two were the left ear. In our study, internal ear anomalies detected in 40 ears were incomplete partition type 2 (mondini deformity) in 8 ears (20%), incomplete partition type 1 in 7 ears (17.5%), isolated enlarged vestibular aqueduct in 6 ears (15%), cochlear hypoplasia in 6 ears (15%), michel anomaly in 5 ears (12.5%), cochlear aplasia in 2 ears (5%), common cavity in 1 ears (2.5%) and VII and VIII cranial nerves agenesis in 1 ears (%2,5) were observed. There were cochlear hypoplasia and enlarged vestibular aquaduct in 4 ears (10%). Vestibule was normal in these patients. No patient had any signs of syndrome. In our study, genetic analysis of 12 of our twenty-two patients with an inner ear anomaly could be concluded. No mutation was detected in six of these 12 patients. SLC26A4 mutation was detected in four patients and GJB2 (CX26) in two patients. One of four patients with SLC26A4 mutation had bilateral hypoplasic cochlea and one had bilateral enlarged vestibular aquaduct. In the other two patients, bilateral enlarged vestibular aquaduct and hypoplasic cochlea were detected. In 2 patients with GJB2 (CX26) mutation, one had bilateral michel anomaly, the other had an incomplete partition type-1 in one ear and an incomplete partition type 2 in one ear. Genetic analysis of the remaining 10 patients continues. Conclusion In our study, inner ear anomalies that we detected in our region were classified. SLC26A4 gene mutations related to inner ear anomalies were detected in 4 patients. In 2 patients with an inner anomaly mutation in the GJB2(CX26) gene associated with non-syndromic hearing loss was detected. No other gene related to inner ear anomaly was detected in our other patients. Key words All genome sequencing, anomaly, gen, hearing loss, inner ear, mutation, sensorineural