Details of Disease

General Information of Disease (ID: DISL7TXC)

• Disease Name: Fuchs' endothelial dystrophy
• Synonyms: Fuchs endothelial corneal dystrophy; Fuchs' corneal dystrophy; FCED; FECD; corneal dystrophy, Fuchs endothelial; Endoepithelial corneal dystrophy; late hereditary endothelial dystrophy; Fuchs' endothelial corneal dystrophy; Fuchs endothelial dystrophy
• Definition: Fuchs endothelial corneal dystrophy (FECD) is the most frequent form of posterior corneal dystrophy and is characterized by excrescences on a thickened Descemet membrane (corneal guttae), generalized corneal edema, with gradually decreased visual acuity.
• Disease Hierarchy:
  DISYKSRF: Genetic disease
  DISR4JFO: Posterior corneal dystrophy
  DIS9BMO3: Corneal endothelial dystrophy
  DISL7TXC: Fuchs' endothelial dystrophy
• Disease Identifiers:
  MONDO ID: MONDO_0005321
  MESH ID: D005642
  UMLS CUI: C0016781
  MedGen ID: 4800
  Orphanet ID: 98974
  SNOMED CT ID: 193839007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 26 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ZEB1	OTEDXTGD	Supportive	Autosomal dominant	[1]
LOXHD1	OTOJ2RHI	Limited	Autosomal dominant	[8]
TMCO3	OTYW1KP2	Limited	Autosomal dominant	[9]
AGBL1	OT8NQLH0	Supportive	Autosomal dominant	[10]
COL8A2	OTASWJ69	Supportive	Autosomal dominant	[11]
SLC4A11	OTMMNQ2E	Supportive	Autosomal dominant	[7]
TCF4	OTB9ASTK	Supportive	Autosomal dominant	[12]
AKAP13	OTOZAR14	Strong	Biomarker	[13]
ARHGAP18	OTYMJP6H	Strong	Altered Expression	[14]
ATP1B1	OTTO6ZP4	Strong	Biomarker	[15]
COL8A1	OTWBTED2	Strong	Genetic Variation	[16]
DMTN	OTDTKPBW	Strong	Genetic Variation	[17]
GATD1	OTLOBJL2	Strong	Genetic Variation	[2]
HLA-DRA	OT7KZMP2	Strong	Biomarker	[18]
KANK4	OT5WC0Q8	Strong	Genetic Variation	[2]
KIF13A	OTSSZGBQ	Strong	Biomarker	[13]
LAMC1	OTIG527N	Strong	Genetic Variation	[2]
LIG3	OT48SKET	Strong	Genetic Variation	[19]
MBNL1	OTOV7J85	Strong	Biomarker	[20]
NEIL1	OTHBU5DJ	Strong	Genetic Variation	[21]
OVOL2	OTFM1GKF	Strong	Biomarker	[22]
PITX2	OTWMXAOY	Strong	Genetic Variation	[23]
PTPRG	OT9N2WOF	Strong	Genetic Variation	[24]
SBK1	OTCO4NEI	Strong	Biomarker	[25]
TGFBI	OTR443C5	Strong	Biomarker	[26]
TNR	OTVJGAFN	Strong	Biomarker	[27]

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CFH	TTUW6OP	Strong	Genetic Variation	[2]
CUL3	TTPCU0Q	Strong	Biomarker	[3]
DMPK	TTZQTY2	Strong	Biomarker	[4]
GPR35	TT254XD	Strong	Biomarker	[5]
MBNL2	TTH9OLG	Strong	Biomarker	[6]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC4A11	DTH2J1G	Supportive	Autosomal dominant	[7]

References

• [1] Missense mutations in TCF8 cause late-onset Fuchs corneal dystrophy and interact with FCD4 on chromosome 9p. Am J Hum Genet. 2010 Jan;86(1):45-53. doi: 10.1016/j.ajhg.2009.12.001. Epub 2009 Dec 31.
• [2] Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.Nat Commun. 2017 Mar 30;8:14898. doi: 10.1038/ncomms14898.
• [3] Decline in DJ-1 and decreased nuclear translocation of Nrf2 in Fuchs endothelial corneal dystrophy.Invest Ophthalmol Vis Sci. 2012 Aug 24;53(9):5806-13. doi: 10.1167/iovs.12-10119.
• [4] Fuchs' Endothelial Corneal Dystrophy in Patients With Myotonic Dystrophy, Type 1.Invest Ophthalmol Vis Sci. 2018 Jun 1;59(7):3053-3057. doi: 10.1167/iovs.17-23160.
• [5] The presence and distribution of G protein-coupled receptor 35 (GPR35) in the human cornea - Evidences from in silico gene expression analysis and immunodetection.Exp Eye Res. 2019 Feb;179:188-192. doi: 10.1016/j.exer.2018.11.011. Epub 2018 Nov 13.
• [6] Trinucleotide Repeat Expansion in the Transcription Factor 4 (TCF4) Gene Leads to Widespread mRNA Splicing Changes in Fuchs' Endothelial Corneal Dystrophy.Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):343-352. doi: 10.1167/iovs.16-20900.
• [7] Missense mutations in the sodium borate cotransporter SLC4A11 cause late-onset Fuchs corneal dystrophy. Hum Mutat. 2010 Nov;31(11):1261-8. doi: 10.1002/humu.21356. Epub 2010 Oct 14.
• [8] Mutations in LOXHD1, a recessive-deafness locus, cause dominant late-onset Fuchs corneal dystrophy. Am J Hum Genet. 2012 Mar 9;90(3):533-9. doi: 10.1016/j.ajhg.2012.01.013. Epub 2012 Feb 16.
• [9] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [10] Mutations in AGBL1 cause dominant late-onset Fuchs corneal dystrophy and alter protein-protein interaction with TCF4. Am J Hum Genet. 2013 Oct 3;93(4):758-64. doi: 10.1016/j.ajhg.2013.08.010.
• [11] Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients. Eye (Lond). 2009 Apr;23(4):895-903. doi: 10.1038/eye.2008.116. Epub 2008 May 9.
• [12] A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy. PLoS One. 2012;7(11):e49083. doi: 10.1371/journal.pone.0049083. Epub 2012 Nov 21.
• [13] Gene Expression and Missplicing in the Corneal Endothelium of Patients With a TCF4 Trinucleotide Repeat Expansion Without Fuchs' Endothelial Corneal Dystrophy.Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3636-3643. doi: 10.1167/iovs.19-27689.
• [14] Transcript profile of cellular senescence-related genes in Fuchs endothelial corneal dystrophy.Exp Eye Res. 2014 Dec;129:13-7. doi: 10.1016/j.exer.2014.10.011. Epub 2014 Oct 11.
• [15] Analysis of candidate genes ZEB1 and LOXHD1 in late-onset Fuchs' endothelial corneal dystrophy in an Indian cohort. Ophthalmic Genet. 2018 Aug;39(4):443-449. doi: 10.1080/13816810.2018.1474367. Epub 2018 May 25.
• [16] No pathogenic mutations identified in the COL8A1 and COL8A2 genes in familial Fuchs corneal dystrophy.Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3787-90. doi: 10.1167/iovs.05-1635.
• [17] Regenerative Therapy for Fuchs Endothelial Corneal Dystrophy.Cornea. 2018 Apr;37(4):523-527. doi: 10.1097/ICO.0000000000001518.
• [18] Immunohistochemical Profiling of Corneas With Fuchs Endothelial Corneal Dystrophy.Cornea. 2017 Jul;36(7):866-874. doi: 10.1097/ICO.0000000000001212.
• [19] Polymorphism of the LIG3 gene in keratoconus and Fuchs endothelial corneal dystrophy.Cell Mol Biol (Noisy-le-grand). 2015 Mar 28;61(1):56-63.
• [20] Fuchs' Endothelial Corneal Dystrophy and RNA Foci in Patients With Myotonic Dystrophy.Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4579-4585. doi: 10.1167/iovs.17-22350.
• [21] Variation in DNA Base Excision Repair Genes in Fuchs Endothelial Corneal Dystrophy.Med Sci Monit. 2015 Sep 21;21:2809-27. doi: 10.12659/MSM.894273.
• [22] Corneal dystrophy-causing SLC4A11 mutants: suitability for folding-correction therapy.Hum Mutat. 2014 Sep;35(9):1082-91. doi: 10.1002/humu.22601. Epub 2014 Jun 28.
• [23] Differing roles for TCF4 and COL8A2 in central corneal thickness and fuchs endothelial corneal dystrophy.PLoS One. 2012;7(10):e46742. doi: 10.1371/journal.pone.0046742. Epub 2012 Oct 23.
• [24] Association of common variants in TCF4 and PTPRG with Fuchs' corneal dystrophy: a systematic review and meta-analysis.PLoS One. 2014 Oct 9;9(10):e109142. doi: 10.1371/journal.pone.0109142. eCollection 2014.
• [25] Results of Femtosecond Laser-Assisted Descemet Stripping Automated Endothelial Keratoplasty.J Ophthalmol. 2017;2017:8984367. doi: 10.1155/2017/8984367. Epub 2017 Jun 11.
• [26] The future of keratoplasty: cell-based therapy, regenerative medicine, bioengineering keratoplasty, gene therapy.Curr Opin Ophthalmol. 2019 Jul;30(4):286-291. doi: 10.1097/ICU.0000000000000573.
• [27] Trinucleotide repeat expansion length as a predictor of the clinical progression of Fuchs' Endothelial Corneal Dystrophy.PLoS One. 2019 Jan 25;14(1):e0210996. doi: 10.1371/journal.pone.0210996. eCollection 2019.