Naoki Okumura1, Vilavun Puangsricharern2,3, Raina Jindasak4, Noriko Koizumi1, Yuya Komori1, Hayashi Ryousuke1, Makiko Nakahara1, Masakazu Nakano5, Hiroko Adachi5, Kei Tashiro5, Kengo Yoshii6, Patchima Chantaren7, Rungnapa Ittiwut8,9, Vorasuk Shotelersuk8,9, Kanya Suphapeetiporn8,9. 1. Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan. 2. Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. vilavun@hotmail.com. 3. Excellence Center for Cornea and Limbal Stem Cell Transplantation, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, 10330, Thailand. vilavun@hotmail.com. 4. Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. 5. Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan. 6. Department of Mathematics and Statistics in Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan. 7. Excellence Center for Cornea and Limbal Stem Cell Transplantation, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, 10330, Thailand. 8. Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. 9. Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, 10330, Thailand.
Abstract
PURPOSE: To evaluate the association of single nucleotide polymorphisms (SNPs) and the intronic expansion of a trinucleotide repeat (TNR) in the TCF4 gene with Fuchs endothelial corneal dystrophy (FECD) in a Thai population. METHODS: In total, 54 Thai FECD patients and 54 controls were recruited for the study. Five SNPs (rs613872, rs2123392, rs17089887, rs1452787, and rs1348047), previously reported to be associated with FECD, were genotyped by direct sequencing. The repeat length was determined by direct sequencing of PCR-amplified DNA (a short tandem repeat; STR assay) and by triplet repeat primed PCR (TP-PCR). RESULTS: Only one of the 54 patients with FECD harboured rs613872 (1.9%). Four SNPs (rs2123392, rs17089887, rs1452787, and rs1348047), which are not rare polymorphisms in the Thai population, were found in approximately half of the patients. Of the 54 patients, 21 (1 homozygous and 20 heterozygous patients; 39%) harboured a TNR ≥ 40, while 33 patients (61%) harboured a TNR < 40. CONCLUSIONS: The association of TNR expansion in TCF4 with FECD is shown for the first time in the Thai population. The intronic TNR expansion identified in various ethnic groups underlines the importance of expansion as a potent pathophysiological cause of FECD.
PURPOSE: To evaluate the association of single nucleotide polymorphisms (SNPs) and the intronic expansion of a trinucleotide repeat (TNR) in the TCF4 gene with Fuchs endothelial corneal dystrophy (FECD) in a Thai population. METHODS: In total, 54 Thai FECD patients and 54 controls were recruited for the study. Five SNPs (rs613872, rs2123392, rs17089887, rs1452787, and rs1348047), previously reported to be associated with FECD, were genotyped by direct sequencing. The repeat length was determined by direct sequencing of PCR-amplified DNA (a short tandem repeat; STR assay) and by triplet repeat primed PCR (TP-PCR). RESULTS: Only one of the 54 patients with FECD harboured rs613872 (1.9%). Four SNPs (rs2123392, rs17089887, rs1452787, and rs1348047), which are not rare polymorphisms in the Thai population, were found in approximately half of the patients. Of the 54 patients, 21 (1 homozygous and 20 heterozygous patients; 39%) harboured a TNR ≥ 40, while 33 patients (61%) harboured a TNR < 40. CONCLUSIONS: The association of TNR expansion in TCF4 with FECD is shown for the first time in the Thai population. The intronic TNR expansion identified in various ethnic groups underlines the importance of expansion as a potent pathophysiological cause of FECD.
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