线粒体A3243G突变导致角膜内皮细胞大小不均。
Mitochondrial A3243G mutation results in corneal endothelial polymegathism.
作者信息
Bakhoum Mathieu F, Wu Wei-Pu, White Eugenia C, Sengillo Jesse D, Sanfilippo Christian, Morcos Marcelle M, Freund K Bailey, Perry Henry D, Sarraf David, Tsang Stephen H
机构信息
Jonas Children's Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory, Columbia University, New York, NY, USA.
Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
出版信息
Graefes Arch Clin Exp Ophthalmol. 2018 Mar;256(3):583-588. doi: 10.1007/s00417-018-3914-z. Epub 2018 Jan 29.
PURPOSE
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.
METHODS
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.
RESULTS
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, the average endothelial cell size was 442 ± 103 μm and the average central corneal thickness (CCT) was 551 ± 33 μm. 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.
CONCLUSIONS
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.
目的
线粒体DNA点突变A3243G可导致一系列综合征，从母系遗传的糖尿病伴耳聋（MIDD）到线粒体脑肌病伴乳酸血症和卒中样发作（MELAS）。眼部表现包括图案状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A3243G的患者进行了镜面生物显微镜分析，以评估角膜内皮异常的相关情况。
方法
我们展示了一个来自两个机构的病例系列。招募了被诊断为与MIDD或MELAS相关的黄斑营养不良以及线粒体DNA点突变A3243G的患者。排除标准包括既往诊断为角膜内皮营养不良或有角膜内皮营养不良的阳性家族史。进行了裂隙灯角膜检查和镜面生物显微镜检查。评估了角膜内皮细胞计数、细胞大小和大小不均一性以及中央角膜厚度。根据临床病史和检查被诊断为MIDD或MELAS的患者，使用焦磷酸测序法对线粒体DNA点突变A3243G进行基因检测。
结果
来自五个不同家庭、具有不同种族背景的五名患者（两名男性和三名女性参与者）符合纳入标准。他们的年龄在41至60岁之间。裂隙灯检查观察到的角膜内皮变化主要为轻度至罕见的角膜小滴。镜面生物显微镜检查主要显示与角膜小滴相关的大小不均一性。平均内皮细胞计数为每平方毫米2358±456个细胞，平均内皮细胞大小为442±103μm，平均中央角膜厚度（CCT）为551±33μm。这些值与普通人群相似。平均变异系数（COV），即细胞大小异质性的指标，为42.0±4.1%。与普通人群相比，患者的平均COV显著高于根据其年龄预测的值。所有患者均无角膜水肿迹象。一名患者有后弹力层前混浊。
结论
在携带线粒体DNA点突变A3243G的患者中存在角膜内皮大小不均一性。这主要与轻度角膜小滴相关。角膜内皮细胞大小不均一性的发现可能是线粒体疾病的一个生物标志物，特别是在携带线粒体DNA A3243G突变的患者中。
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