Mitochondrial A3243G mutation results in corneal endothelial polymegathism
Mitochondrial A3243G mutation results in corneal endothelial polymegathism
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DOI：
10.1007/s00417-018-3914-z
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发表时间：
2018-03-01
影响因子：
2.7
通讯作者：
Tsang, Stephen H.
中科院分区：
文献类型：
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作者：
Bakhoum, Mathieu F.;Wu, Wei-Pu;Tsang, Stephen H.
线粒体DNA点突变A3243 G导致从MIDD到MELAS的一系列综合征。眼部表现包括模式性黄斑营养不良和中心凹周围同心性萎缩。鉴于角膜内皮细胞的高代谢需求，我们对携带线粒体DNA点突变A3243 G的患者进行了角膜内皮生物显微镜分析，以评估角膜内皮异常的相关存在。招募诊断为MIDD或MELAS相关黄斑营养不良和线粒体DNA点突变A3243 G的患者。排除标准包括先前诊断为角膜内皮营养不良或有阳性家族史。进行裂隙灯角膜检查和角膜内皮生物显微镜检查。评估角膜内皮细胞计数、细胞大小和多巨化以及中央角膜厚度。采用焦磷酸测序法对临床诊断为MIDD或MELAS的患者进行线粒体DNA点突变A3243 G的基因检测，结果发现来自5个不同家族、不同种族背景的5例患者（2男3女）均符合纳入标准。年龄41 ~ 60岁。使用裂隙灯检查观察到的角膜内皮变化主要为轻度至罕见滴状。镜面反射生物显微镜主要显示与滴状体相关的多巨畸形。平均内皮细胞计数为2358 +/- 456个细胞/mm 2，平均内皮细胞大小为442 +/- 103 μ m 2，平均中央角膜厚度（CCT）为551 +/- 33 μ m。这些值与平均人口的值相似。平均变异系数（COV）是细胞大小异质性的指数，为42.0 +/-4.1%。与平均人群相比，平均COV显著高于患者年龄的预测值。所有患者均无角膜水肿体征。1例患者出现前后弹力层混浊，在线粒体DNA点突变A3243 G的患者中，存在角膜内皮多肥大。这主要与轻度滴状痛有关。角膜内皮细胞多形性可能是线粒体疾病的生物标志物，特别是在线粒体DNA A3243 G突变的患者中。
The mitochondrial DNA point mutation A3243G leads to a spectrum of syndromes ranging from MIDD to MELAS. Ocular manifestations include pattern macular dystrophy and concentric perifoveal atrophy. Given the high metabolic demand of corneal endothelial cells, we performed specular biomicroscopy analysis in patients harboring the mitochondrial DNA point mutation A3243G to assess for the associated presence of corneal endothelial abnormalities.We present a case series with participants from two institutions. Patients diagnosed with macular dystrophy associated with MIDD or MELAS, and the mitochondrial DNA point mutation A3243G were recruited. Exclusion criteria included a prior diagnosis, or a positive family history, of endothelial corneal dystrophy. Slit-lamp corneal examination and specular biomicroscopy were performed. Corneal endothelial cell count, cell size and polymegathism, and central corneal thickness were assessed. Patients diagnosed with MIDD or MELAS based on clinical history and examination were genetically tested for the mitochondrial DNA point mutation A3243G using pyrosequencing.Five patients (two male and three female participants) from five different families, and with different ethnic backgrounds, met the inclusion criteria. Their ages ranged from 41 to 60 years. Corneal endothelial changes observed using slit-lamp examination were primarily mild to rare guttata. Specular biomicroscopy displayed mainly polymegathism associated with guttata. The average endothelial cell count was 2358 +/- 456 cells per mm(2), the average endothelial cell size was 442 +/- 103 mu m(2) and the average central corneal thickness (CCT) was 551 +/- 33 mu m. These values were similar to that of the average population. The average coefficient of variation (COV), an index of heterogeneity in cell size, was 42.0 +/- 4.1%. When compared to the average population, the average COV was significantly higher than predicted for the patients' age. None of the patients had signs of corneal edema. One patient had a pre-Descemet's opacity.In patients with the mitochondrial DNA point mutation A3243G, corneal endothelial polymegathism is present. This is mainly associated with mild guttata. The findings of corneal endothelial cell polymegathism may be a biomarker of mitochondrial disease, specifically in patients with the mitochondrial DNA A3243G mutation.