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

Eric D Wieben, Ross A. Aleff, Xiaojia Tang, Krishna R Kalari, Leo J. Maguire, Sanjay V. Patel, Keith Baratz, Michael P Fautsch

Research output: Contribution to journalArticle

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Abstract

Fuchs Endothelial Corneal Dystrophy (FECD) is a late onset, autosomal dominant eye disease that can lead to loss of vision. Expansion of a CTG trinucleotide repeat in the third intron of the transcription factor 4 (TCF4) gene is highly associated with FECD. However, only about 75% of FECD patients in the northern European population possess an expansion of this repeat. The remaining FECD cases appear to be associated with variants in other genes. To better understand the pathophysiology of this disease, we compared gene expression profiles of corneal endothelium from FECD patients with an expanded trinucleotide repeat (RE+) to those that do not have a repeat expansion (RE-). Comparative analysis of these two cohorts showed widespread RNA mis-splicing in RE+, but not in RE- samples. Quantitatively, we identified 39 genes in which expression was significantly different between RE+ and RE- samples. Examination of the mutation profiles in the RE- samples did not find any mutations in genes previously associated with FECD, but did reveal one sample with a rare variant of laminin subunit gamma 1 (LAMC1) and three samples with rare variants in the gene coding for the mitochondrial protein peripheral-type benzodiazepine receptor-associated protein 1 (TSPOAP1).

Original languageEnglish (US)
Article numbere0200005
JournalPLoS One
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2018

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Fuchs' Endothelial Dystrophy
Trinucleotide Repeat Expansion
Trinucleotide Repeats
Corneal Endothelium
endothelium
Gene expression
Transcription Factors
transcription factors
microsatellite repeats
Gene Expression
Genes
gene expression
sampling
genes
eye diseases
mutation
benzodiazepines
laminin
RNA Splicing
pathophysiology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Gene expression in the corneal endothelium of fuchs endothelial corneal dystrophy patients with and without expansion of a trinucleotide repeat in TCF4. / Wieben, Eric D; Aleff, Ross A.; Tang, Xiaojia; Kalari, Krishna R; Maguire, Leo J.; Patel, Sanjay V.; Baratz, Keith; Fautsch, Michael P.

In: PLoS One, Vol. 13, No. 7, e0200005, 01.07.2018.

Research output: Contribution to journalArticle

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abstract = "Fuchs Endothelial Corneal Dystrophy (FECD) is a late onset, autosomal dominant eye disease that can lead to loss of vision. Expansion of a CTG trinucleotide repeat in the third intron of the transcription factor 4 (TCF4) gene is highly associated with FECD. However, only about 75{\%} of FECD patients in the northern European population possess an expansion of this repeat. The remaining FECD cases appear to be associated with variants in other genes. To better understand the pathophysiology of this disease, we compared gene expression profiles of corneal endothelium from FECD patients with an expanded trinucleotide repeat (RE+) to those that do not have a repeat expansion (RE-). Comparative analysis of these two cohorts showed widespread RNA mis-splicing in RE+, but not in RE- samples. Quantitatively, we identified 39 genes in which expression was significantly different between RE+ and RE- samples. Examination of the mutation profiles in the RE- samples did not find any mutations in genes previously associated with FECD, but did reveal one sample with a rare variant of laminin subunit gamma 1 (LAMC1) and three samples with rare variants in the gene coding for the mitochondrial protein peripheral-type benzodiazepine receptor-associated protein 1 (TSPOAP1).",
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