Should Patients with Kearns-Sayre Syndrome and Corneal Endothelial Failure Be Genotyped for a TCF4 Trinucleotide Repeat, Commonly Associated with Fuchs Endothelial Corneal Dystrophy?
Should Patients with Kearns-Sayre Syndrome and Corneal Endothelial Failure Be Genotyped for a TCF4 Trinucleotide Repeat, Commonly Associated with Fuchs Endothelial Corneal Dystrophy?
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DOI：
10.3390/genes12121918
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发表时间：
2021-11-29
期刊：
影响因子：
3.5
通讯作者：
Liskova P
中科院分区：
文献类型：
--
作者：
Dudakova L;Skalicka P;Davidson AE;Sadan AN;Chylova M;Jahnova H;Anteneova N;Tesarova M;Honzik T;Liskova P
本研究的目的是描述与Kearns-Sayre综合征（KSS）频谱的情况下，眼表型，并确定角膜内皮细胞功能障碍是否可以归因于其他已知的不同的遗传原因。在此，从血液中提取基因组DNA并进行外显子组测序。通过桑格测序筛选与角膜内皮营养不良有关的非编码基因区域。此外，使用短串联重复序列分析对位于TCF 4内含子内的重复扩增（称为CTG 18.1）进行基因分型。KSS谱的诊断是基于上睑下垂、慢性进行性眼外肌麻痹、色素性视网膜病变、听力损失和肌无力的存在，这进一步得到~6.5 kb mtDNA缺失检测的支持。在33岁时，先证者的最佳矫正视力下降到右眼0.04，左眼0.2。罕见的眼部发现包括右眼和左眼明显角膜水肿，中央角膜厚度分别为824和844 µm。未发现与角膜内皮营养不良相关的致病基因变异。此外，CTG18.1基因型为12/33，这超过了先前确定的角膜内皮细胞中出现毒性RNA病灶的临界阈值。
The aim of this study was to describe the ocular phenotype in a case with Kearns-Sayre syndrome (KSS) spectrum and to determine if corneal endothelial cell dysfunction could be attributed to other known distinct genetic causes. Herein, genomic DNA was extracted from blood and exome sequencing was performed. Non-coding gene regions implicated in corneal endothelial dystrophies were screened by Sanger sequencing. In addition, a repeat expansion situated within an intron of TCF4 (termed CTG18.1) was genotyped using the short tandem repeat assay. The diagnosis of KSS spectrum was based on the presence of ptosis, chronic progressive external ophthalmoplegia, pigmentary retinopathy, hearing loss, and muscle weakness, which were further supported by the detection of ~6.5 kb mtDNA deletion. At the age of 33 years, the proband’s best corrected visual acuity was reduced to 0.04 in the right eye and 0.2 in the left eye. Rare ocular findings included marked corneal oedema with central corneal thickness of 824 and 844 µm in the right and left eye, respectively. No pathogenic variants in the genes, which are associated with corneal endothelial dystrophies, were identified. Furthermore, the CTG18.1 genotype was 12/33, which exceeds a previously determined critical threshold for toxic RNA foci appearance in corneal endothelial cells.
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影响因子：
3.7
作者：
Wieben ED;Aleff RA;Tosakulwong N;Butz ML;Highsmith WE;Edwards AO;Baratz KH
通讯作者：
Baratz KH
影响因子：
64.8
作者：
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通讯作者：
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影响因子：
2.3
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影响因子：
3.3
作者：
Anteneová N;Kelifová S;Kolářová H;Vondráčková A;Tóthová I;Lišková P;Magner M;Zámečník J;Hansíková H;Zeman J;Tesařová M;Honzík T
通讯作者：
Honzík T
影响因子：
5.2
作者：
Bene, J;Nádasi, E;Melegh, B
通讯作者：
Melegh, B