scholarly journals Expansion of trinucleotide CTG repeats in the TCF4 gene as a marker of fuchs’ endothelial corneal dystrophy

2019 ◽  
Vol 12 (2) ◽  
pp. 11-18
Author(s):  
Sanasar S. Papanyan ◽  
Sergey Yu. Astakhov ◽  
Vladimir D. Nazarov ◽  
Sergey V. Lapin ◽  
Sergey A. Novikov ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Trinucleotide Repeat ◽  
Corneal Edema ◽  
Corneal Dystrophy ◽  
Triplet Repeat ◽  
Triplet Repeats ◽  
Ctg Repeats ◽  
Laboratory Marker ◽  
The Third ◽  
Ctg Repeat

Fuchs’ endothelial corneal dystrophy (FECD) is an inherited severe and progressive disease, characte­rized by endothelial cell density decrease and increasing corneal edema. FECD development may be linked to expanded trinucleotide repeat, CTG, in the third intron of the TCF4 gene. The study focuses on estimating the prevalence of expanded CTG repeat in TCF4 gene in the Russian population, in patients with normal cornea and in patients with FECD (by applying triplet repeat PCR technique and capillary electrophoresis). 51 patients with FECD and 38 patients with normal cornea were examined. The estimation of the number of CTG triplet repeats in TCF4 gene determination is the veracious laboratory marker of FECD.

scholarly journals Transcriptionally Repressive Chromatin Remodelling and CpG Methylation in the Presence of Expanded CTG-Repeats at the DM1 Locus

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Judith Rixt Brouwer ◽  
Aline Huguet ◽  
Annie Nicole ◽  
Arnold Munnich ◽  
Geneviève Gourdon
Keyword(s):  
Transgenic Mice ◽  
Trinucleotide Repeat ◽  
Cpg Methylation ◽  
Chromatin Remodelling ◽  
Ctcf Binding ◽  
Type I ◽  
Repeat Instability ◽  
Ctg Repeats ◽  
Repressive Chromatin ◽  
Ctg Repeat

An expanded CTG-repeat in the 3′ UTR of theDMPKgene is responsible for myotonic dystrophy type I (DM1). Somatic and intergenerational instability cause the disease to become more severe during life and in subsequent generations. Evidence is accumulating that trinucleotide repeat instability and disease progression involve aberrant chromatin dynamics. We explored the chromatin environment in relation to expanded CTG-repeat tracts in hearts from transgenic mice carrying the DM1 locus with different repeat lengths. Using bisulfite sequencing we detected abundant CpG methylation in the regions flanking the expanded CTG-repeat. CpG methylation was postulated to affect CTCF binding but we found that CTCF binding is not affected by CTG-repeat length in our transgenic mice. We detected significantly decreasedDMPKsense andSIX5transcript expression levels in mice with expanded CTG-repeats. Expression of the DM1 antisense transcript was barely affected by CTG-repeat expansion. In line with altered gene expression, ChIP studies revealed a locally less active chromatin conformation around the expanded CTG-repeat, namely, decreased enrichment of active histone mark H3K9/14Ac and increased H3K9Me3 enrichment (repressive chromatin mark). We also observed binding of PCNA around the repeats, a candidate that could launch chromatin remodelling cascades at expanded repeats, ultimately affecting gene transcription and repeat instability.

scholarly journals Increased Instability of Human CTG Repeat Tracts on Yeast Artificial Chromosomes during Gametogenesis

1999 ◽  
Vol 19 (6) ◽  
pp. 4153-4158 ◽  
Author(s):  
Haim Cohen ◽  
Dorothy D. Sears ◽  
Drora Zenvirth ◽  
Philip Hieter ◽  
Giora Simchen
Keyword(s):  
Genetic Analysis ◽  
Trinucleotide Repeat ◽  
Mitotic Division ◽  
Human Diseases ◽  
Ctg Repeats ◽  
Artificial Chromosomes ◽  
Repeat Tract ◽  
Yeast Artificial Chromosomes ◽  
Dmpk Gene ◽  
Ctg Repeat

ABSTRACT Expansion of trinucleotide repeat tracts has been shown to be associated with numerous human diseases. The mechanism and timing of the expansion events are poorly understood, however. We show that CTG repeats, associated with the human DMPK gene and implanted in two homologous yeast artificial chromosomes (YACs), are very unstable. The instability is 6 to 10 times more pronounced in meiosis than during mitotic division. The influence of meiosis on instability is 4.4 times greater when the second YAC with a repeat tract is not present. Most of the changes we observed in trinucleotide repeat tracts are large contractions of 21 to 50 repeats. The orientation of the insert with the repeats has no effect on the frequency and distribution of the contractions. In our experiments, expansions were found almost exclusively during gametogenesis. Genetic analysis of segregating markers among meiotic progeny excluded unequal crossover as the mechanism for instability. These unique patterns have novel implications for possible mechanisms of repeat instability.

scholarly journals Impact of TCF4 Repeat Number on Resolution of Corneal Edema after Descemet’s Stripping Only in Fuchs Dystrophy: A Pilot Study

Vision ◽  
2021 ◽  
Vol 5 (4) ◽  
pp. 47
Author(s):  
Natasha Spiteri ◽  
Nino Hirnschall ◽  
Katherine van Bysterveldt ◽  
Alec Lin Hou ◽  
Gregory Moloney ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Corneal Edema ◽  
Corneal Dystrophy ◽  
Partial Least Square ◽  
Least Square ◽  
Partial Least Square Regression ◽  
Ctg Repeats ◽  
Increased Risk ◽  
Transcription Factor 4 ◽  
Allele Repeat

Purpose: To investigate whether Fuchs endothelial corneal dystrophy (FECD) genotype, specifically transcription factor 4 (TCF4) CTG triplet repeat “load” predicts time to clearance following Descemet’s Stripping Only (DSO). Methods: This prospective, interventional trial was conducted on consecutive FECD patients undergoing DSO. Genetic analysis using patients’ saliva was performed to assess the extent of CTG expansion using short tandem repeat analysis, corroborated gel electrophoresis and Sanger sequencing. Polymerase chain reaction and bidirectional Sanger sequencing was undertaken. Partial least square regression and logistic regression modelling was used to evaluate the predictive power of TCF4 repeats on corneal clearance. Results: Of 11 eyes of 11 patients, 8 showed complete corneal clearance. For these 8 patients, mean TCF4 allele repeat was 24.8 (SD: 23.7, range: 11–63) and 63.4 (SD: 30.3; range: 11–97), respectively. In total, 9/11 (81.8%) had expanded CTG repeats (>40) in one allele. In cases with an allele repeat ≥80, there was a significantly increased risk of corneal non-clearance (odds ratio 18.2, p = 0.009). Conclusion: Whilst it was not possible to predict time to corneal clearance based on CTG repeats, there is a significant correlation between allele repeats and achievement of corneal clearance.

Features of the course and treatment of glaucoma during pregnancy

2020 ◽  
Vol 98 (3) ◽  
pp. 178-184
Author(s):  
T. V. Chernyakova ◽  
A. Yu. Brezhnev ◽  
I. R. Gazizova ◽  
A. V. Kuroyedov ◽  
A. V. Seleznev
Keyword(s):  
Pregnant Women ◽  
Laser Treatment ◽  
Progressive Disease ◽  
Clinical Course ◽  
The Other ◽  
Third Trimester ◽  
The Third ◽  
Chronic Progressive Disease ◽  
Hypotensive Therapy ◽  
Eye Pressure

In the review we have integrated all up-to-date knowledge concerning clinical course and treatment of glaucoma among pregnant women to help specialists choose a proper policy of treatment for such a complicated group of patients. Glaucoma is a chronic progressive disease. It rarely occurs among childbearing aged women. Nevertheless the probability to manage pregnant patients having glaucoma has been recently increasing. The situation is complicated by the fact that there are no recommendations on how to treat glaucoma among pregnant women. As we know, eye pressure is progressively going down from the first to the third trimester, so we often have to correct hypotensive therapy. Besides, it is necessary to take into account the effect of applied medicines on mother health and evaluate possible teratogenic complications for a fetus. The only medicine against glaucoma which belongs to category B according to FDA classification is brimonidine. Medicines of the other groups should be prescribed with care. Laser treatment or surgery may also be a relevant decision when monitoring patients who are planning pregnancy or just bearing a child. Such treatment should be also accompanied by medicines.

scholarly journals Trinucleotide repeat expansion length as a predictor of the clinical progression of Fuchs’ Endothelial Corneal Dystrophy

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0210996 ◽  
Author(s):  
Yu Qiang Soh ◽  
Gary Peh Swee Lim ◽  
Hla Myint Htoon ◽  
Xin Gong ◽  
V. Vinod Mootha ◽  
...  
Keyword(s):  
Trinucleotide Repeat ◽  
Corneal Dystrophy ◽  
Repeat Expansion ◽  
Clinical Progression ◽  
Trinucleotide Repeat Expansion

scholarly journals Trinucleotide repeat expansion in the transcription factor 4 (TCF4) gene in Thai patients with Fuchs endothelial corneal dystrophy

Eye ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 880-885 ◽  
Author(s):  
Naoki Okumura ◽  
Vilavun Puangsricharern ◽  
Raina Jindasak ◽  
Noriko Koizumi ◽  
Yuya Komori ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Trinucleotide Repeat ◽  
Corneal Dystrophy ◽  
Repeat Expansion ◽  
Trinucleotide Repeat Expansion ◽  
Transcription Factor 4

scholarly journals Gene expression in the corneal endothelium of Fuchs endothelial corneal dystrophy patients with and without expansion of a trinucleotide repeat in TCF4

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0200005 ◽  
Author(s):  
Eric D. Wieben ◽  
Ross A. Aleff ◽  
Xiaojia Tang ◽  
Krishna R. Kalari ◽  
Leo J. Maguire ◽  
...  
Keyword(s):  
Gene Expression ◽  
Corneal Endothelium ◽  
Trinucleotide Repeat ◽  
Corneal Dystrophy

Aphasia and Chorea in General Paralysis

1875 ◽  
Vol 21 (95) ◽  
pp. 421-424 ◽  
Author(s):  
T. S. Clouston
Keyword(s):  
Progressive Disease ◽  
General Paralysis ◽  
The Third ◽  
One Stage ◽  
Short Period

The general progressive disease in the structure of the nervous centres, and the steady deterioration of their functions, that constitute by far the chief part of general paralysis, are attended in their course in some cases by various nervous symptoms that closely imitate many of the neuroses of sensibility and motion; such as neuralgia, amaurosis, locomotor ataxy, glosso-pharyngeal paralysis, hemiplegia, apoplexy and epilepsy. Indeed, it is not uncommon for cases of the disease to be diagnosed as epilepsy and glosso-pharyngeal paralysis. I have lately had three cases of the disease under my care, in two of which the ordinary symptoms of aphasia were present for a short period in one stage of the disease, and in the third the symptoms of unilateral chorea were well marked.

scholarly journals Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients With Fuchs Endothelial Corneal Dystrophy

Cornea ◽  
2019 ◽  
Vol 38 (7) ◽  
pp. 799-805 ◽  
Author(s):  
Naoki Okumura ◽  
Ryousuke Hayashi ◽  
Masakazu Nakano ◽  
Kei Tashiro ◽  
Kengo Yoshii ◽  
...  
Keyword(s):  
Trinucleotide Repeat ◽  
Corneal Dystrophy ◽  
Repeat Expansion ◽  
Trinucleotide Repeat Expansion
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