FECD3 TCF4

Late-onset Fuchs endothelial corneal dystrophy (FECD) is a degenerative disorder ... distinguished from other corneal disorders by the progressive formation of guttae¹.

Prevalence

4.5 100

~4/100 (over 40)¹; 5/100². Predominantly in women (~75%)³. Although studies on the prevalence of FECD worldwide are limited, the disorder is thought to be more common in Eurasian populations⁴, with its corneal manifestations documented in 11% of females and 7% of males in Reykjavik, Iceland, 8.5 % of Singapore Chinese, and 5.5% of Japanese⁵. Uncommon/rare in Saudi Arabia, Singaporean Chinese, and Japan⁶.

Age of Onset Details

Typical: 40-59⁷; Range: 32⁸- 70⁹.

Locus

hg19

chr18:53253386-53253458

hg38

chr18:55586155-55586227

t2t

chr18:55789234-55789288

Details

Most controls have <40 repeats while majority of patients have >50 repeats; penetrance is <100%, as unaffected individuals have been documented with >80 repeats and alleles of affected individuals range from 12-2600^10,9. Expansions are causative in approximately 70% of disease cases¹⁰.

Mechanism

GoF

Sequestration of MBNL1 in RNA foci, similar to the mechanism underlying myotonic dystrophy-1¹¹. Variation in RAN translation¹².

Year

2012¹³

Location in Gene

Intron 1

Gene Strand

Alleles

Ref. Motif

CAG

Pathogenic (ref.)

CAG

Pathogenic (gene)

CTG

gnomAD

References

Direct supporting references for info on this page.

omim:613267

E2-2 protein and Fuchs's corneal dystrophy.

Keith H,Baratz, Nirubol,Tosakulwong, Euijung,Ryu, William L,Brown, Kari,Branham, Wei,Chen, Khoa D,Tran, Katharina E,Schmid-Kubista, John R,Heckenlively, Anand,Swaroop, Goncalo,Abecasis, Kent R,Bailey, Albert O,Edwards

The New England journal of medicine · 2010-08-25

pmid:20825314

Clinical study of Fuchs corneal endothelial dystrophy leading to penetrating keratoplasty: a 30-year experience.

Natalie A,Afshari, Aaron B,Pittard, Adnan,Siddiqui, Gordon K,Klintworth

Archives of ophthalmology (Chicago, Ill. : 1960) · 2006-06-01

pmid:16769829

Correlation of Severity of Fuchs Endothelial Corneal Dystrophy With Triplet Repeat Expansion in TCF4.

Ahmed Z,Soliman, Chao,Xing, Salma H,Radwan, Xin,Gong, V Vinod,Mootha

JAMA ophthalmology · 2015-12-01

pmid:26401622

TCF4 Triplet Repeat Expansion and Nuclear RNA Foci in Fuchs' Endothelial Corneal Dystrophy.

V Vinod,Mootha, Imran,Hussain, Khrishen,Cunnusamy, Eric,Graham, Xin,Gong, Sudha,Neelam, Chao,Xing, Ralf,Kittler, W Matthew,Petroll

Investigative ophthalmology & visual science · 2015-02-26

pmid:25722209

Orphanet: Fuchs endothelial corneal dystrophy

orphanet:98974

Pharmacological profile of non-hydroxylated and ether derivatives of the potent D2-selective agonist N-0437.

J M,Jansen, I,den Daas, H,Rollema, P J,Swart, P G,Tepper, J B,de Vries, A S,Horn

Naunyn-Schmiedeberg's archives of pharmacology · 1991-02-01

pmid:1676829

Replication of the TCF4 intronic variant in late-onset Fuchs corneal dystrophy and evidence of independence from the FCD2 locus.

S Amer,Riazuddin, Elyse J,McGlumphy, William S,Yeo, Jiangxia,Wang, Nicholas,Katsanis, John D,Gottsch

Investigative ophthalmology & visual science · 2011-04-27

pmid:21245398

Comprehensive assessment of genetic variants within TCF4 in Fuchs' endothelial corneal dystrophy.

Eric D,Wieben, Ross A,Aleff, Bruce W,Eckloff, Elizabeth J,Atkinson, Saurabh,Baheti, Sumit,Middha, William L,Brown, Sanjay V,Patel, Jean-Pierre A,Kocher, Keith H,Baratz

Investigative ophthalmology & visual science · 2014-08-28

pmid:25168903

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

RNA toxicity and missplicing in the common eye disease fuchs endothelial corneal dystrophy.

Jintang,Du, Ross A,Aleff, Elisabetta,Soragni, Krishna,Kalari, Jinfu,Nie, Xiaojia,Tang, Jaime,Davila, Jean-Pierre,Kocher, Sanjay V,Patel, Joel M,Gottesfeld, Keith H,Baratz, Eric D,Wieben

The Journal of biological chemistry · 2015-01-15

pmid:25593321

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784

A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy.

Eric D,Wieben, Ross A,Aleff, Nirubol,Tosakulwong, Malinda L,Butz, W Edward,Highsmith, Albert O,Edwards, Keith H,Baratz

PloS one · 2012-11-21

pmid:23185296

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Prevalence of Transcription Factor 4 Gene Triplet Repeat Expansion Associated with Fuchs' Endothelial Corneal Dystrophy in the United States and Global Populations.

Xunzhi,Zhang, Ashwani,Kumar, Xin,Gong, Chao,Xing, V Vinod,Mootha

Ophthalmology science · 2024-08-30

pmid:39669694

Insights into the causes and consequences of DNA repeat expansions from 700,000 biobank participants.

Margaux L A,Hujoel, Robert E,Handsaker, Nolan,Kamitaki, Ronen E,Mukamel, Simone,Rubinacci, Pier F,Palamara, Steven A,McCarroll, Po-Ru,Loh

bioRxiv : the preprint server for biology · 2024-11-26

pmid:39651202

TCF4 trinucleotide repeat expansions and UV irradiation increase susceptibility to ferroptosis in Fuchs endothelial corneal dystrophy.

Sanjib,Saha, Jessica M,Skeie, Gregory A,Schmidt, Tim,Eggleston, Hanna,Shevalye, Christopher S,Sales, Pornpoj,Phruttiwanichakun, Apurva,Dusane, Matthew G,Field, Tommy A,Rinkoski, Michael P,Fautsch, Keith H,Baratz, Madhuparna,Roy, Albert S,Jun, Chandler,Pendleton, Aliasger K,Salem, Mark A,Greiner

Redox biology · 2024-09-10

pmid:39332053

Change in Visual Acuity of Patients With Fuchs Endothelial Corneal Dystrophy Over 1 Year.

Oliver,Dorado-Cortez, Emmanuel,Crouzet, Marie Caroline,Trone, Philippe,Gain, Zhiguo,He, Hanielle,Vaitinadapoule, Marielle,Mentek, Frédéric,Mascarelli, Sylvain,Poinard, Mari,Yasunaga, Go,Nishiuchi, Noriko,Koizumi, Naoki,Okumura, Gilles,Thuret

Cornea · 2024-07-09

pmid:39288343

Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping.

Christina,Zarouchlioti, Stephanie,Efthymiou, Stefano,Facchini, Natalia,Dominik, Nihar,Bhattacharyya, Siyin,Liu, Marcos Abreu,Costa, Anita,Szabo, Amanda N,Sadan, Albert S,Jun, Enrico,Bugiardini, Henry,Houlden, Andrea,Cortese, Pavlina,Skalicka, Lubica,Dudakova, Kirithika,Muthusamy, Michael E,Cheetham, Alison J,Hardcastle, Petra,Liskova, Stephen J,Tuft, Alice E,Davidson

EBioMedicine · 2024-09-14

pmid:39278108

Increased Risk of Glaucoma in Fuchs Endothelial Corneal Dystrophy Is Independent of TCF4 Trinucleotide Repeat Expansion.

Chao,Xing, Sara,Schultis, Vladyslav,Bondar, Xin,Gong, Jess T,Whitson, V Vinod,Mootha

Cornea · 2024-09-03

pmid:39231626

Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease.

Nihar,Bhattacharyya, Niuzheng,Chai, Nathaniel J,Hafford-Tear, Amanda N,Sadan, Anita,Szabo, Christina,Zarouchlioti, Jana,Jedlickova, Szi Kay,Leung, Tianyi,Liao, Lubica,Dudakova, Pavlina,Skalicka, Mohit,Parekh, Ismail,Moghul, Aaron R,Jeffries, Michael E,Cheetham, Kirithika,Muthusamy, Alison J,Hardcastle, Nikolas,Pontikos, Petra,Liskova, Stephen J,Tuft, Alice E,Davidson

PLoS genetics · 2024-05-07

pmid:38713708

Transcription factor 4 promotes increased corneal endothelial cellular migration by altering microtubules in Fuchs endothelial corneal dystrophy.

Judy,Yan, Shanti,Mehta, Keya,Patel, Narisa,Dhupar, Ness,Little, Stephan,Ong Tone

Scientific reports · 2024-05-04

pmid:38704483

Comparison of Scheimpflug and Anterior Segment Optical Coherence Tomography Imaging Parameters for Japanese Patients With Fuchs Endothelial Corneal Dystrophy With and Without TCF4 Repeat Expansions.

Sayo,Maeno, Yoshinori,Oie, Ryota,Koto, Nozomi,Nishida, Arisa,Yamashita, Michika,Yoshioka, Chifune,Kai, Takeshi,Soma, Shizuka,Koh, Masahito,Yoshihara, Ryo,Kawasaki, Vishal,Jhanji, Masayuki,Nakamori, Motokazu,Tsujikawa, Kohji,Nishida

Cornea · 2024-02-01

pmid:38300219