Effect of trinucleotide repeat expansion on the expression of TCF4 mRNA in Fuchs' endothelial corneal dystrophy

Okumura, Naoki, Hayashi, Ryosuke, Nakano, Masakazu, Yoshii, Kengo, Tashiro, Kei, Sato, Takahiko, Blake, Derek J. ORCID: https://orcid.org/0000-0002-5005-4731, Aleff, Ross, Butz, Malinda, Highsmith, Edward W., Wieben, Eric D., Fautsch, Michael P., Baratz, Keith H., Komori, Yuya, Nakahara, Makiko, Tourtas, Theofilos, Schlötzer-Schrehardt, Ursula, Kruse, Friedrich and Koizumi, Noriko 2019. Effect of trinucleotide repeat expansion on the expression of TCF4 mRNA in Fuchs' endothelial corneal dystrophy. Investigative Ophthalmology & Visual Science 60 (2) , p. 779. 10.1167/iovs.18-25760

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Abstract

Purpose: CTG trinucleotide repeat (TNR) expansion is frequently found in transcription factor 4 (TCF4) in Fuchs' endothelial corneal dystrophy (FECD), though the effect of TNR expansion on FECD pathophysiology remains unclear. The purpose of this study was to evaluate the effect of TNR expansion on TCF4 expression in corneal endothelium of patients with FECD. Methods: Peripheral blood DNA and Descemet membrane with corneal endothelium were obtained from 203 German patients with FECD. The CTG TNR repeat length in TCF4 was determined by short tandem repeat (STR) assays and Southern blotting using genomic DNA. Genotyping of rs613872 in TCF4 was performed by PCR. TCF4 mRNA levels in corneal endothelium were evaluated by quantitative PCR using three different probes. Control corneal endothelial samples were obtained from 35 non-FECD subjects. Results: The STR assay and Southern blotting showed that 162 of the 203 patients with FECD (80%) harbored CTG trinucleotide repeat lengths larger than 50. Quantitative PCR using all three probes demonstrated that TCF4 mRNA is significantly upregulated in the corneal endothelium of patients with FECD, regardless of the presence of TNR expansion. However, the length of the TNR tended to show a positive correlation with TCF4 expression level. No correlation was shown between the genotype of TCF4 SNP, rs613872, and the level of TCF4 expression. Conclusions: Our findings showed that TCF4 mRNA is upregulated in the corneal endothelium of patients with FECD. Further studies on the effects of TCF4 upregulation on corneal endothelial cell function will aid in understanding the pathophysiology of FECD.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Association for Research in Vision and Ophthalmology
ISSN:	0146-0404
Date of First Compliant Deposit:	1 March 2019
Date of Acceptance:	1 February 2019
Last Modified:	08 May 2023 04:00
URI:	https://orca.cardiff.ac.uk/id/eprint/120131

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