Transcriptomic analysis implicates the involvement of RBM20 in Fuchs' endothelial corneal dystrophy with TCF4 repeat...

Late-onset Fuchs' endothelial corneal dystrophy (FECD) is a degenerative disease of cornea manifesting during the fourth decade of life or later. An intronic trinucleotide repeat expansion (CTG18.1) in the transcription factor 4 (TCF4) gene is estimated to account for two thirds of FECD cases. There is a high degree of similarity between the transcriptomic profiles with (RE+) and without (RE-) the expansion. The molecular mechanisms of FECD and the difference between the two FECD types remain to be elucidated.

Analyses were based on publicly available RNA sequencing datasets of human corneal endothelial tissues. We compared the distributions of differentially expressed genes between the RE+ and RE- transcriptomic profiles for a given co-expression network module. Upstream regulator analysis, alternative splicing analysis, motif enrichment analysis, and structure prediction were conducted.

The expression levels of ribonucleic acid binding motif protein 20 (RBM20) were upregulated in both RE+ cases and RE+ controls. Consistently, its motif was enriched in the skipped exon events of RE+ subjects compared with RE- subjects. There were skipped exon events in three genes-DST, FNBP1 and SORBS1- consistently identified in RE+ subjects out of the documented RBM20 target genes in the literature.

RBM20 may represent an RE+ specific factor in the pathogenesis of FECD. The increase of RBM20 expression in RE+ individuals may contribute to the disease by repressing the inclusion of exons.