Audio profiles in mitochondrial deafness m.1555A>G and m.3243A>G show distinct differences.
Audio profiles in mitochondrial deafness m.1555A>G and m.3243A>G show distinct differences.
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DOI：
10.12659/msm.890965
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发表时间：
2015-03-06
期刊：
影响因子：
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通讯作者：
Płoski R
中科院分区：
文献类型：
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作者：
Iwanicka-Pronicka K;Pollak A;Skórka A;Lechowicz U;Korniszewski L;Westfal P;Skarżyński H;Płoski R
听力丧失是线粒体疾病最常见的症状之一。然而，与mtDNA中不同分子缺陷相关的听力学表型尚未得到很好的表征。对1499名年龄在5-40岁、病因不明的听力损失非近亲患者进行mtDNA突变筛查。为进一步分析，选择m.1555A>G和m.3243A>G患者。采用纯音测听法评估患者的听力状况。对m.1555A>G和m.3243A>G突变携带者的听图模式（每个检测频率下的听阈水平）进行统计学比较。我们发现20例患者m.1555A>G突变阳性，16例患者m.3243A>G突变阳性。在我们的队列中，上述转换的频率分别为1.33%和1.06%。17名携带突变基因的受影响家庭成员被纳入研究。m.1555A突变>G患者的典型听力学曲线呈滑坡型，而m.3243A突变>G患者的典型听力学曲线在较高频率处呈轻微向下倾斜的音调曲线（平坦曲线）。差异有统计学意义。m.1555A>G患者比m.3243A>G患者更早出现听力损失（分别为12.5岁和26岁）。两组分别有11例和4例氨基糖苷类药物，所有病例均出现突发性听力下降。线粒体耳聋患者的听力图模式可能提示mtDNA突变的定位。听力差异的发病机制有待进一步研究。
Hearing loss is one of the most common symptoms of mitochondrial disorders. However, audiological phenotypes associated with different molecular defects in mtDNA are not yet well characterized. A large cohort of 1499 nonconsanguineous patients aged 5–40 years with hearing loss of unknown etiology was screened for mutations in mtDNA. For further analysis, patients harboring m.1555A>G and m.3243A>G were selected. Hearing status of the patients was assessed by pure tone audiometry. Patterns of audiograms (hearing threshold levels at each examined frequency) were statistically compared among the carriers of the m.1555A>G and the m.3243A>G mutations. We identified 20 patients positive for m.1555A>G mutation and 16 patients positive for m.3243A>G change. The frequency of the above transitions was calculated in our cohort as 1.33% and 1.06%, respectively. Seventeen affected family members carrying the mutations were included into the study. Typical shape of the audiograms in patients with m.1555A>G mutation presented a ski-slope pattern, whereas the audiometric curves among the m.3243A>G individuals had a pantonal shape (a flat curve) with slight downward sloping at the higher frequencies. The differences were statistically significant. The onset of hearing loss was noted earlier among m.1555A>G than m.3243A>G patients (12.5 and 26 years, respectively). Aminoglycoside administration was declared in both groups in 11 and 4 cases respectively, and caused abrupt hearing deterioration in all cases. A pattern of audiogram in patients with mitochondrial deafness may suggest a localization of mtDNA mutation. The pathogenesis of the audiometric differences needs further study.