Yaprak E. ÇIRÇIR, Armağan İNCESULU, Mustafa TEKİN

Sensörinöral işitme kaybı olan kişilerde mitokondriyal 12S rRNA MTRNR1 geninin taranması

Amaç: Aminoglikozit kullanma öyküsü bulunan vebulunmayan sensörinöral işitme kayıplı olgulardamitokondriyal DNA 12S rRNA MTRNR1 genindekimutasyonlar araştırıldı.Hastalar ve Yöntemler: Araştırmaya sendromik olmayan sensörinöral işitme kayıplı 70 olgu alındı. On bir bireyin öyküsünde işitme kaybı gelişmeden önce aminoglikozit kullanımı olduğu öğrenildi. Bütün olgularda önce GJB2 connexin 26 geni tarandı ve normal bulundu. m.1555A>G mutasyonunun araştırılmasında PCR-RFLP yöntemi kullanıldı. Daha sonra MTRNR1 geni PCR-TTGE ile tarandı. Bu taramada bant farklılığı gösteren örneklere doğrudandizi analizi yapıldı.Bulgular: Aminoglikozit kullanımı öyküsü olan 11hastanın birinde m.1555A>G mutasyonu bulundu.Aminoglikozit kullanım öyküsü olmayan ve sensörinöral işitme kaybı olan iki kişide m.750A>G polimorfizmi saptandı. Diğer olgularda, patojenik olabilecekbaşka bir baz değişimine rastlanmadı.Sonuç: Aminoglikozit ototoksisitesine yatkınlık yapan en önemli DNA değişikliği olan m.1555A>G mutasyonu dışında Türkiye’de yaygın bir mitokondriyal12S rRNA mutasyonu bulunamadı. Ancak, bu geningeniş serilerde taranması daha az görülen değişikliklerin saptanmasını sağlayabilir

Anahtar Kelimeler:

Aminoglikozit, sensorinöral işitme kaybı/etyoloji, RNA/genetik

Screening of the mitochondrial 12S rRNA MTRNR1 gene in probands with sensorineural hearing loss

Objectives: We investigated mitochondrial DNA 12S rRNA MTRNR1 gene mutations as a cause of hearing loss in probands with or without a history of aminoglycoside use.Patients and Methods: The study included 70 patients 40 females, 30 males; age range 3 to 42 years with nonsyndromic sensorineural hearing loss. Eleven probands had a history of aminoglyco side use before the onset of hearing loss. AH cases were first screened and found to be negative for the GJB2 connexin 26 gene mutations. The m.1555A>G mutation was screened using the PCR- RFLP technique. The entire 12S rRNA gene was later screened with the PCR-TTGE technique fol- lowed by direct sequencing.Results: Of 11 patients with a history of aminogly coside use, one patient was found to have the m.1555A>G mutation. Two probands with no history of aminoglycoside use exhibited the m.750A>G polymorphism. No pathogenic base substitutions were detected in the remaining patients.Conclusion: Apart from the common aminoglyco side ototoxicity-related DNA change, m.1555A>G, we could not identify a common mitochondrial 12S rRNA mutation associated with hearing loss in Turkey. Screening of larger series may document rare alterations.

Keywords:

Aminoglycosides hearing loss, sensorineural/etiology, RNA/genetics,

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