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Abstract：
Fuchs endothelial corneal dystrophy (FECD) is caused by a corneal endothelial cell loss, leading to corneal edema and visual impairment. The most significant genetic risk factor for FECD is an expansion of the CTG18.1 locus in transcription factor 4 (TCF4). The current treatment for severe FECD is corneal transplantation, with Descemet stripping automated keratoplasty (DSAEK) as a common surgical method. Although successful in most cases, the risk for transplant failure due to diverse causes must be considered. In this study, we investigated if presence of TCF4 CTG18.1 expansion with more than 31 (n ≥ 31) repeats in donated corneal grafts could be a reason for corneal transplant failure after DSAEK. For this, nine consecutively failed DSAEK corneal grafts were genotyped for CTG18.1 repeat length. One-sided Mann-Whitney U test was performed to evaluate if failed DSAEK corneal grafts had longer CTG18.1 repeats than healthy controls from the same population. All failed corneal grafts had CTG18.1 n ≤ 27 with a median of 18 (IQR 8.0) repeats for the longest allele. There was no statistical difference in CTG18.1 repeat lengths between failed corneal grafts and the geographically matched healthy control group. In conclusion, none of the nine failed corneal grafts in our material had CTG18.1 repeat lengths ≥ 31, a cut-off known to have a biological relevance in FECD. Thus, our results suggest that the assessment of donors and inspection of the corneal tissue before the decision for procurement is sufficient, in terms of recognizing FECD in the donor.
摘要：
Fuchs内皮角膜营养不良（FECD）是由角膜内皮细胞丢失引起的，导致角膜水肿和视力障碍。FECD最重要的遗传风险因素是转录因子4（TCF4）中CTG18.1基因座的扩展。目前严重FECD的治疗方法是角膜移植，以Descemet剥离自动角膜移植术（DSAEK）作为一种常见的手术方法。虽然在大多数情况下是成功的，必须考虑由于多种原因导致移植失败的风险。在这项研究中,我们调查了TCF4CTG18.1在捐赠的角膜移植物中重复超过31次(n≥31次)的扩增是否可能是DSAEK后角膜移植失败的原因.为此，对9例连续失败的DSAEK角膜移植物进行CTG18.1重复长度的基因分型。进行单侧Mann-WhitneyU检验以评估失败的DSAEK角膜移植物是否比来自相同人群的健康对照具有更长的CTG18.1重复。所有失败的角膜移植物的CTG18.1n≤27，最长等位基因的中位数为18（IQR8.0）重复。失败的角膜移植物和地理匹配的健康对照组之间的CTG18.1重复长度没有统计学差异。总之,我们的材料中的9个失败的角膜移植物中没有一个具有CTG18.1重复长度≥31，这是已知在FECD中具有生物学相关性的截止值。因此，我们的结果表明，在决定采购之前，对供体的评估和对角膜组织的检查是足够的，在承认捐赠者的FECD方面。
