Fuchs Endothelial Corneal Dystrophy: Strong Association with rs613872 Not Paralleled by Changes in Corneal Endothelial<i>TCF4</i>mRNA Level

Ołdak, Monika; Ruszkowska, Ewelina; Udziela, Monika; Oziębło, Dominika; Binczyk, E.; Ścieżyńska, Aneta; Płoski, Rafał; Szaflik, Jacek P.

doi:10.1155/2015/640234

Cited by 25 publications

(29 citation statements)

References 23 publications

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“…The FECD-associated expanded TGC repeat in TCF4 is also an intronic repeat. However, our differential gene expression analysis data (unpublished) and reported studies [ 28 , 43 ] have shown that expression levels of TCF4 mRNA in the corneal endothelium between FECD cases and controls and between carriers of risk and non-risk alleles of SNP rs613872 are similar indicating that transcription inhibition likely is not involved in the pathogenesis of FECD.…”

Section: Discussionmentioning

confidence: 60%

TGC repeat expansion in the TCF4 gene increases the risk of Fuchs’ endothelial corneal dystrophy in Australian cases

et al. 2017

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Fuchs’ endothelial corneal dystrophy (FECD) is a progressive, vision impairing disease. Common single nucleotide polymorphisms (SNPs) and a trinucleotide repeat polymorphism, thymine-guanine-cytosine (TGC), in the TCF4 gene have been associated with the risk of FECD in some populations. We previously reported association of SNPs in TCF4 with FECD risk in the Australian population. The aim of this study was to determine whether TGC repeat polymorphism in TCF4 is associated with FECD in the Australian population. In 189 unrelated Australian cases with advanced late-onset FECD and 183 matched controls, the TGC repeat polymorphism located in intron 3 of TCF4 was genotyped using a short tandem repeat (STR) assay. The repeat length was verified by direct sequencing in selected homozygous carriers. We found significant association between the expanded TGC repeat (≥ 40 repeats) in TCF4 and advanced FECD (P = 2.58 × 10−22; OR = 15.66 (95% CI: 7.79–31.49)). Genotypic analysis showed that 51% of cases (97) compared to 5% of controls (9) were heterozygous or homozygous for the expanded repeat allele. Furthermore, the repeat expansion showed stronger association than the most significantly associated SNP, rs613872, in TCF4, with the disease in the Australian cohort. This and haplotype analysis of both the polymorphisms suggest that considering both the polymorphisms together rather than either of the two alone would better predict susceptibility to FECD in the Australian population. This is the first study to report association of the TGC trinucleotide repeat expansion in TCF4 with advanced FECD in the Australian population.

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Section: Discussionmentioning

confidence: 60%

TGC repeat expansion in the TCF4 gene increases the risk of Fuchs’ endothelial corneal dystrophy in Australian cases

et al. 2017

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“…15,17 TCF4 mutations cause Pitt-Hopkins syndrome, (PTHS) 18 and TCF4 gene variants have been strongly associated with the development of Fuchs endothelial corneal dystrophy (FECD). 19 To our knowledge, there have been no reports of patients with SAK in combination with PTHS or FECD. None of the patients with SAK in this family had any symptoms related to either PTHS or FECD.…”

Section: Discussionmentioning

confidence: 96%

“…Transcription factor 4 appears to function through Wnt‐dependent and ‐independent pathways and may impact on epithelial homeostasis . TCF4 mutations cause Pitt‐Hopkins syndrome, (PTHS) and TCF4 gene variants have been strongly associated with the development of Fuchs endothelial corneal dystrophy (FECD) . To our knowledge, there have been no reports of patients with SAK in combination with PTHS or FECD.…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing identifies a TCF4 mutation in a Chinese pedigree with symmetrical acral keratoderma

Chen

Sun

Zeng

et al. 2017

Acad Dermatol Venereol

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“…penetrance and different degree of correlation between ethnicities. 1,28,102,104,123,138 The second most frequent cause of endothelial decompensation is pseudophakic bullous keratopathy (PBK). Despite the major advances in cataract surgery and ophthalmic viscosurgical devices, phacoemulsification can damage the endothelial layer and result in corneal decompensation.…”

Section: Common Endothelial Diseasesmentioning

confidence: 99%

A review of the evidence for in vivo corneal endothelial regeneration

Bogerd

Dhubhghaill

Koppen

et al. 2018

Survey of Ophthalmology

107

104

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Human corneal endothelium has long been thought to be a nonmitotic cell layer with no endogenous reparative potential. Pathologies that damage endothelial function result in corneal decompensation and, if untreated, blindness. The mainstay of treatment involves partial or complete corneal replacement, amounting to 40% of all corneal transplants performed worldwide. We summarize the case reports describing complications postoperatively in the form of (sub)total graft detachment and those resulting in postoperative bare stroma. Complications during cataract and glaucoma surgeries leading to an uncovered posterior cornea are also included. We discuss the newer treatment strategies that are alternatives for current Descemet membrane endothelial keratoplasty and Descemet stripping automated endothelial keratoplasty, including partial grafts and stripping of the diseased cell layer. In more than half of the cases reviewed, corneal transparency returned despite incomplete or no corneal endothelial cell transplantation. We question the existing paradigm concerning corneal endothelial wound healing in vivo. The data support further clinical study to determine the safety of simple descemethorexis in central endothelial pathologies, such as Fuchs endothelial corneal dystrophy, where presence of healthy peripheral cells may allow successful corneal recompensation without the need for donor cells.

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Fuchs Endothelial Corneal Dystrophy: Strong Association with rs613872 Not Paralleled by Changes in Corneal EndothelialTCF4mRNA Level

Cited by 25 publications

References 23 publications

TGC repeat expansion in the TCF4 gene increases the risk of Fuchs’ endothelial corneal dystrophy in Australian cases

TGC repeat expansion in the TCF4 gene increases the risk of Fuchs’ endothelial corneal dystrophy in Australian cases

Exome sequencing identifies a TCF4 mutation in a Chinese pedigree with symmetrical acral keratoderma

A review of the evidence for in vivo corneal endothelial regeneration

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