Kistik Fibrozis Hastalarında Mitokondriyal DNA Mutasyonları ile Aminoglikozit Ototoksisitesi Arasındaki İlişkinin Araştırılması

Abstract

Cystic fibrosis is an autosomal recessive genetic disease seen in Caucasians and caused by mutations in the CFTR gene. Aminoglycosides used in the treatment of cystic fibrosis cause hearing loss as a side effect in patients. It is known that mutations m.1555A>G, m.1494C>T and m.1095T>C in the MTRNR1 gene in mitochondrial DNA cause aminoglycoside-associated hearing loss. For this reason, screening patients for mutations before administering aminoglycoside treatment is of great importance in cystic fibrosis patients. Our aim in this thesis study is to investigate the frequency of mutations associated with aminoglycoside ototoxicity in the MTRNR1 gene in cystic fibrosis patients. 119 retrospectively selected patients with or without a history of aminoglycoside use were included in our study. Patients were classified according to clinical features such as otorhinolaryngological findings, audiological findings and aminoglycoside use. Mutations were analyzed using the PCR-RFLP method. Aminoglycoside use was found in 97 of 119 patients; it is not present in 22 patients. High-frequency sensorineural hearing loss was detected in 13 patients using aminoglycosides. 119 patients were screened for mutations and no mutations were detected. Despite aminoglycoside ototoxicity, MTRNR1 gene mutation screenings are not routinely performed in our country. Mutation screenings in cystic fibrosis patients before aminoglycoside treatment are planned to be included in patient diagnosis and monitoring guidelines. By evaluating clinical parameters together, a personalized treatment approach will be developed for cystic fibrosis patients.