Trinucleotide Repeat Expansion in the TCF4 Gene in Fuchs' Endothelial Corneal Dystrophy in Japanese

• Published in: Investigative ophthalmology & visual science Vol. 56; no. 8; p. 4865
• Main Authors: Nakano, Masakazu, Okumura, Naoki, Nakagawa, Hiroko, Koizumi, Noriko, Ikeda, Yoko, Ueno, Morio, Yoshii, Kengo, Adachi, Hiroko, Aleff, Ross A., Butz, Malinda L., Highsmith, W. Edward, Tashiro, Kei, Wieben, Eric D., Kinoshita, Shigeru, Baratz, Keith H.
• Format: Journal Article
• Language: English
• Published: United States 01.07.2015
• Subjects: Aged; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Blotting, Southern; DNA - genetics; Female; Fuchs' Endothelial Dystrophy - genetics; Fuchs' Endothelial Dystrophy - metabolism; Genetic Predisposition to Disease; Genotype; Humans; Introns; Japan; Male; Microsatellite Repeats; Polymerase Chain Reaction; Retrospective Studies; Transcription Factor 4; Transcription Factors - genetics; Transcription Factors - metabolism; Trinucleotide Repeat Expansion
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.15-17082

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. 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. 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. 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.