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Gene expression in the corneal endothelium of Fuchs endothelial corneal dystrophy patients with and without expansion of a trinucleotide repeat in TCF4
- Source :
- PLoS ONE, PLoS ONE, Vol 13, Iss 7, p e0200005 (2018)
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
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).
- Subjects :
- Male
0301 basic medicine
Molecular biology
lcsh:Medicine
Gene Expression
Artificial Gene Amplification and Extension
medicine.disease_cause
Polymerase Chain Reaction
Biochemistry
Cornea
Transcription Factor 4
Sequencing techniques
Trinucleotide Repeats
Gene expression
Medicine and Health Sciences
lcsh:Science
Aged, 80 and over
Mutation
Multidisciplinary
Endothelium, Corneal
RNA sequencing
TCF4
Middle Aged
3. Good health
Nucleic acids
Female
Anatomy
Research Article
Corneal endothelium
Ocular Anatomy
Biology
03 medical and health sciences
Ocular System
Genetics
medicine
Humans
Endothelium
Gene
Aged
Gene amplification
Gene Expression Profiling
lcsh:R
Fuchs' Endothelial Dystrophy
Intron
Genetic Variation
Biology and Life Sciences
RNA
Research and analysis methods
Alternative Splicing
RNA amplification
Molecular biology techniques
030104 developmental biology
RNA processing
Cardiovascular Anatomy
lcsh:Q
Trinucleotide Repeat Expansion
Trinucleotide repeat expansion
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....b18f2a90cbe431f7b08141ea0c26bc36