PURPOSE: Fuchs dystrophy is the leading indication of corneal transplantation in the United States. A CTG18.1 trinucleotide repeat in TCF4 correlates with increased severity in Fuchs dystrophy; however, quantitative estimates of increased transplantation risk, including effects of age and sex, are unclear. METHODS: In a tertiary institution clinical practice, 574 participants were enrolled in a longitudinal study of Fuchs dystrophy after slit-lamp biomicroscopy confirmed significant central guttae and/or corneal transplantation in both eyes. We documented clinical history, examination findings, and demographic information. We acquired blood samples, extracted DNA, and sequenced the CTG18.1 trinucleotide repeat in TCF4. In this retrospective case-control study, the number of participants with triplet expansion, defined as greater than 40 CTG repeats, and transplantation status were assessed. Kaplan-Meier estimates of timing and transplantation events were produced. The Cox proportional hazard regression model was used to assess the relationship between age, sex, triplet expansion, and surgery. RESULTS: A total of 106 participants (18.5%) previously underwent corneal transplantation in at least 1 eye at the time of initial evaluation. A higher proportion of individuals harboring allele expansion had undergone transplantation (78/357, 21.8%) compared with those without the expanded allele (28/217, 12.9%), a significant association (P = 0.007). The log-rank test demonstrates a significant difference in survival function over time (P = 0.027), with a hazard ratio of 1.64 (95% confidence interval, 1.05-2.55). CONCLUSIONS: Expansion of the TCF4 CTG trinucleotide repeat was associated with 1.64 times higher likelihood of corneal transplantation at a given age in patients with Fuchs dystrophy.
PURPOSE:Fuchs dystrophy is the leading indication of corneal transplantation in the United States. A CTG18.1 trinucleotide repeat in TCF4 correlates with increased severity in Fuchs dystrophy; however, quantitative estimates of increased transplantation risk, including effects of age and sex, are unclear. METHODS: In a tertiary institution clinical practice, 574 participants were enrolled in a longitudinal study of Fuchs dystrophy after slit-lamp biomicroscopy confirmed significant central guttae and/or corneal transplantation in both eyes. We documented clinical history, examination findings, and demographic information. We acquired blood samples, extracted DNA, and sequenced the CTG18.1 trinucleotide repeat in TCF4. In this retrospective case-control study, the number of participants with triplet expansion, defined as greater than 40 CTG repeats, and transplantation status were assessed. Kaplan-Meier estimates of timing and transplantation events were produced. The Cox proportional hazard regression model was used to assess the relationship between age, sex, triplet expansion, and surgery. RESULTS: A total of 106 participants (18.5%) previously underwent corneal transplantation in at least 1 eye at the time of initial evaluation. A higher proportion of individuals harboring allele expansion had undergone transplantation (78/357, 21.8%) compared with those without the expanded allele (28/217, 12.9%), a significant association (P = 0.007). The log-rank test demonstrates a significant difference in survival function over time (P = 0.027), with a hazard ratio of 1.64 (95% confidence interval, 1.05-2.55). CONCLUSIONS: Expansion of the TCF4CTGtrinucleotide repeat was associated with 1.64 times higher likelihood of corneal transplantation at a given age in patients with Fuchs dystrophy.
Authors: Olof H Sundin; Albert S Jun; Karl W Broman; Sammy H Liu; Siobhan E Sheehan; Elizabeth C L Vito; Walter J Stark; John D Gottsch Journal: Invest Ophthalmol Vis Sci Date: 2006-01 Impact factor: 4.799
Authors: Olof H Sundin; Karl W Broman; Howard H Chang; Elizabeth C L Vito; Walter J Stark; John D Gottsch Journal: Invest Ophthalmol Vis Sci Date: 2006-09 Impact factor: 4.799
Authors: S Amer Riazuddin; Eranga N Vithana; Li-Fong Seet; Yangjian Liu; Amr Al-Saif; Li Wei Koh; Yee Meng Heng; Tin Aung; Danielle N Meadows; Allen O Eghrari; John D Gottsch; Nicholas Katsanis Journal: Hum Mutat Date: 2010-10-14 Impact factor: 4.878
Authors: 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 Journal: N Engl J Med Date: 2010-08-25 Impact factor: 91.245
Authors: Shivakumar Vasanth; Allen O Eghrari; Briana C Gapsis; Jiangxia Wang; Nicolas F Haller; Walter J Stark; Nicholas Katsanis; S Amer Riazuddin; John D Gottsch Journal: Invest Ophthalmol Vis Sci Date: 2015-07 Impact factor: 4.799
Authors: S Amer Riazuddin; Norann A Zaghloul; Amr Al-Saif; Lisa Davey; Bill H Diplas; Danielle N Meadows; Allen O Eghrari; Mollie A Minear; Yi-Ju Li; Gordon K Klintworth; Natalie Afshari; Simon G Gregory; John D Gottsch; Nicholas Katsanis Journal: Am J Hum Genet Date: 2009-12-31 Impact factor: 11.025
Authors: Elisabetta Soragni; Lina Petrosyan; Tommy A Rinkoski; Eric D Wieben; Keith H Baratz; Michael P Fautsch; Joel M Gottesfeld Journal: Invest Ophthalmol Vis Sci Date: 2018-04-01 Impact factor: 4.799
Authors: Timothy T Xu; Yi-Ju Li; Natalie A Afshari; Ross A Aleff; Tommy A Rinkoski; Sanjay V Patel; Leo J Maguire; Albert O Edwards; William L Brown; Michael P Fautsch; Eric D Wieben; Keith H Baratz Journal: Invest Ophthalmol Vis Sci Date: 2021-01-04 Impact factor: 4.799
Authors: Allen O Eghrari; Sina Vahedi; Natalie A Afshari; S Amer Riazuddin; John D Gottsch Journal: Invest Ophthalmol Vis Sci Date: 2017-12-01 Impact factor: 4.799
Authors: Michael P Fautsch; Eric D Wieben; Keith H Baratz; Nihar Bhattacharyya; Amanda N Sadan; Nathaniel J Hafford-Tear; Stephen J Tuft; Alice E Davidson Journal: Prog Retin Eye Res Date: 2020-07-28 Impact factor: 21.198