Lower Fractions of TCF4 Transcripts Spanning over the CTG18.1 Trinucleotide Repeat in Human Corneal Endothelium.

Irina Golovleva,Berit Byström,Andreas Viberg,Ida Maria Westin

doi:10.3390/genes12122006

Irina Golovleva, Berit Byström + Show 2 more

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https://doi.org/10.3390/genes12122006

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Journal: Genes	Publication Date: Dec 17, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Umeå University

Abstract

Fuchs’ endothelial corneal dystrophy (FECD) is a bilateral disease of the cornea caused by gradual loss of corneal endothelial cells. Late-onset FECD is strongly associated with the CTG18.1 trinucleotide repeat expansion in the Transcription Factor 4 gene (TCF4), which forms RNA nuclear foci in corneal endothelial cells. To date, 46 RefSeq transcripts of TCF4 are annotated by the National Center of Biotechnology information (NCBI), however the effect of the CTG18.1 expansion on expression of alternative TCF4 transcripts is not completely understood. To investigate this, we used droplet digital PCR for quantification of TCF4 transcripts spanning over the CTG18.1 and transcripts with transcription start sites immediately downstream of the CTG18.1. TCF4 expression was analysed in corneal endothelium and in whole blood of FECD patients with and without CTG18.1 expansion, in non-FECD controls without CTG18.1 expansion, and in five additional control tissues. Subtle changes in transcription levels in groups of TCF4 transcripts were detected. In corneal endothelium, we found a lower fraction of transcripts spanning over the CTG18.1 tract compared to all other tissues investigated.

Highlights

Fuchs endothelial corneal dystrophy (FECD) is a bilateral disease of the cornea caused by gradual loss of corneal endothelial cells
In this study we aimed to investigate if the Transcription Factor 4 gene (TCF4) (CTG)n expansion (n > 40) (TCF4+), present in the majority of FECD patients affects the mRNA expression of TCF4 transcripts spanning over the CTG18.1 or transcripts with transcription start sites (TSS) immediately at the 3 -end of the (CTG)n
We investigated if the TCF4 (CTG)n expansion (n > 40) present in the majority of FECD patients affects the mRNA expression of TCF4 transcripts spanning over the CTG18.1 repeat or transcripts with TSS immediately at the 3 -end of the (CTG)n

Summary

Introduction

Fuchs endothelial corneal dystrophy (FECD) is a bilateral disease of the cornea caused by gradual loss of corneal endothelial cells. Early-onset FECD caused by missense mutations in COL8A2 gene usually starts at a young age and advances to late stage in the fourth decade of life [1,2,3]. First symptoms of late-onset FECD are usually seen at mid-40 s and later, and the disease was first associated with an intronic SNP, rs613872 in Transcription Factor 4 gene (TCF4) back in 2010 [4]. Functional analyses of the TCF4 RNA transcripts spanning over the expanded CTG18.1 have revealed that the repeat expansion tract folds into secondary structures termed RNA nuclear foci in corneal endothelial cells [16,17,18]

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