Fuchs Endothelial Corneal Dystrophy (TCF4)
| Dred_ID | RD00052 |
| OMIM ID | 602272 |
| Disease name | Fuchs Endothelial Corneal Dystrophy |
| Alternative names | Fcd2 Locus Corneal Dystrophy, Fuchs Endothelial, Late-onset |
| Category | Genetic diseases |
| Phenotype | OMIM: Late-onset Fuchs endothelial corneal dystrophy (FECD) is a degenerative disorder affecting roughly 4% of the population older than 40 years. It is distinguished from other corneal disorders by the progressive formation of guttae, which are microscopic refractile excrescences of the Descemet membrane, a collagen-rich basal lamina secreted by the corneal endothelium. From onset, it usually takes 2 decades for FECD to impair endothelial cell function seriously, leading to stromal edema and impaired vision. |
| Miscellaneouse | usually sporadic onset by 3rd or 4th decade (earlier onset rare) greater expression in females female to male ratio, 1:1 |
| Prevalence | N/A [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | TCF4 |
| Alias symbols | E2-2; ITF2; PTHS; SEF2; ITF-2; SEF-2; TCF-4; SEF2-1; SEF2-1A; SEF2-1B; SEF2-1D; bHLHb19 |
| Gene name | transcription factor 4 |
| Gene map locus | 18q21.1; chr18:55,222,185-55,664,787(-) |
| Ensembl Gene ID | ENSG00000196628 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | This gene encodes transcription factor 4, a basic helix-loop-helix transcription factor. The encoded protein recognizes an Ephrussi-box ('E-box') binding site ('CANNTG') - a motif first identified in immunoglobulin enhancers. This gene is broadly expressed, and may play an important role in nervous system development. Defects in this gene are a cause of Pitt-Hopkins syndrome. In addition, an intronic CTG repeat normally numbering 10-37 repeat units can expand to >50 repeat units and cause Fuchs endothelial corneal dystrophy. Multiple alternatively spliced transcript variants that encode different proteins have been described. [provided by RefSeq, Jul 2016] |
| Repeat unit | CTG |
| Normal repeat copies | 5-31 |
| Pathogenic repeat copies | ≥51 |
| Gene | TCF4 |
| Repeat location | intron |
| Chromosome locus | chr18:55586153-55586227 (-) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | Mootha et al. (2015) identified nuclear CUG-repeat RNA foci in corneal endothelial cells from FECD patients carrying the CTG18.1 expansion; however, no RNA foci were seen in controls. Because there was no significant difference in TCF4 expression between carriers and noncarriers of the expansion, the authors concluded that rather than haploinsufficiency of TCF4, toxic RNA is the primary mechanism of disease in FECD. [By OMIM] |
| Pathway annotation | Reactome, KEGG |
| PMID | 29966009 |
| Authors | Wieben ED, Aleff RA, Fautsch MP |
| Title | Gene expression in the corneal endothelium of Fuchs endothelial corneal dystrophy patients with and without expansion of a trinucleotide repeat in TCF4 |
| Journal | PLoS One. |
| Year | 2018 |
| PMID | 29325021 |
| Authors | Hu J, Rong Z, Mootha VV |
| Title | Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy |
| Journal | Hum Mol Genet. |
| Year | 2018 |