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

Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4865-9. doi: 10.1167/iovs.15-17082.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors
  • DNA