Masakazu Nakano1, Naoki Okumura2, Hiroko Nakagawa3, Noriko Koizumi4, Yoko Ikeda3, Morio Ueno3, Kengo Yoshii5, Hiroko Adachi1, Ross A Aleff6, Malinda L Butz7, W Edward Highsmith7, Kei Tashiro1, Eric D Wieben6, Shigeru Kinoshita3, Keith H Baratz8. 1. Department of Genomic Medical Sciences Kyoto Prefectural University of Medicine, Kyoto, Japan. 2. Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan 3Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 3. Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 4. Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan. 5. Department of Medical Statistics, Kyoto Prefectural University of Medicine, Kyoto, Japan. 6. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, United States. 7. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States. 8. Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States.
Abstract
PURPOSE: The purpose of this study was to evaluate the association between the intronic expansion of a trinucleotide repeat (TNR) in the TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Japanese population. METHODS: Forty-seven Japanese FECD patients and 96 age-matched controls were recruited. FECD patients and controls were examined by slit-lamp and noncontact specular microscopy. The repeat length was determined by direct sequencing and short tandem repeat assay of PCR-amplified DNA and Southern blotting of unamplified DNA. RESULTS: A TNR expansion, defined as >50 CTG repeats in the TCF4 gene was identified in 12 of 47 FECD cases (26%) and 0 of 96 controls (0%; P < 0.001). Sensitivity and specificity in this study were 26% and 100%, respectively. The clinical characteristics of FECD patients with TNR expansion were not distinct from those without TNR expansion. CONCLUSIONS: These findings show for the first time in a Japanese population the association of the TNR expansion in TCF4 with FECD. In contrast to Caucasian cohorts in whom the TNR expansion is present in most patients with FECD, a CTG expansion is present in a minority of Japanese subjects, indicating other genetic variants as common causes of phenotypically identical disease in this population.
PURPOSE: The purpose of this study was to evaluate the association between the intronic expansion of a trinucleotide repeat (TNR) in the TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Japanese population. METHODS: Forty-seven Japanese FECDpatients and 96 age-matched controls were recruited. FECDpatients and controls were examined by slit-lamp and noncontact specular microscopy. The repeat length was determined by direct sequencing and short tandem repeat assay of PCR-amplified DNA and Southern blotting of unamplified DNA. RESULTS: A TNR expansion, defined as >50 CTG repeats in the TCF4 gene was identified in 12 of 47 FECD cases (26%) and 0 of 96 controls (0%; P < 0.001). Sensitivity and specificity in this study were 26% and 100%, respectively. The clinical characteristics of FECDpatients with TNR expansion were not distinct from those without TNR expansion. CONCLUSIONS: These findings show for the first time in a Japanese population the association of the TNR expansion in TCF4 with FECD. In contrast to Caucasian cohorts in whom the TNR expansion is present in most patients with FECD, a CTG expansion is present in a minority of Japanese subjects, indicating other genetic variants as common causes of phenotypically identical disease in this population.
Authors: Naoki Okumura; Ryousuke Hayashi; Masakazu Nakano; Kei Tashiro; Kengo Yoshii; Ross Aleff; Malinda Butz; Edward W Highsmith; Eric D Wieben; Michael P Fautsch; Keith H Baratz; Yuya Komori; Emi Ueda; Makiko Nakahara; Julia Weller; Theofilos Tourtas; Ursula Schlötzer-Schrehardt; Friedrich Kruse; Noriko Koizumi Journal: Cornea Date: 2019-07 Impact factor: 2.651
Authors: Stephan Ong Tone; Viridiana Kocaba; Myriam Böhm; Adam Wylegala; Tomas L White; Ula V Jurkunas Journal: Prog Retin Eye Res Date: 2020-05-08 Impact factor: 21.198