台州地区耳聋相关的线粒体12S rRNA C1494T突变筛查

Screening for deafness-associated mitochondrial C1494T mutation in Taizhou area

目的探讨线粒体12SrRNA基因C1494T突变和耳聋的相关性,为了耳聋的防治提供理论依据。方法在台州地区收集耳聋患者200例以及100例性别和年龄相仿的正常对照,使用聚合酶链反应(PCR)和测序法筛选线粒体C1494T突变,并进行临床和分子遗传学的评估。结果测序结果显示有2名耳聋患者携带同质性的C1494T突变,检出率为1%,其中只有1位患者具有明显的家族遗传。该家系的外显率较高,线粒体全基因组测序发现携带tRNASer(UCN)T7505C突变,该突变在进化上高度保守,可能会引起线粒体功能损伤,进而加剧了耳聋的外显率和表现度。结论线粒体C1494T突变是药物性耳聋相关的重要分子基础,继发突变T7505C可能会影响C1494T突变的表型表达,因此,本研究对耳聋的防治有重要的临床指导意义。

Objective:To explore the influence of mitochondrial 12 S rRNA C1494 T mutations in the clinical expression of maternally inherited aminoglycoside-induced deafness,and provided valuable information for prevention and diagnosis of hearing loss.Methods:We enrolled 200 deaf patients and 100 age and gender-matched healthy controls from Taizhou area,we further used PCR and sequence analysis to screen the mitochondrial C1494 T mutation,in addition,we performed the clinical and molecular characterization of the C1494 T deaf patients.Results:Sequence data indicated that there were 2 deafness patients carrying the homoplasmic C1494 T mutation(1%).However,only one patient has the family history of hearing loss.This Chinese pedigree exhibited a high penetrance of hearing loss,analysis of the complete mitochondrial genome showed the presence of tRNASer(UCN)T7505 C mutation,which was very conserved between different species,and may cause the mitochondrial dysfunction,therefore,increase the penetrance and expressivity of hearing loss-associated C1494 T mutation.Conclusions:Mitochondrial C1494 T mutation may be the important molecular basis for hearing loss,secondary T7505 C mutation may influence the clinical manifestation of C1494 T mutation,thus,our study is very useful for prevention and treatment of hearing loss.