Association and Familial Segregation of CTG18.1 Trinucleotide Repeat Expansion of TCF4 Gene in Fuchs' Endothelial Corneal Dystrophy

摘要: Purpose We tested the association between two intronic polymorphisms (CTG18.1 and rs613872) in TCF4 Fuchs' endothelial corneal dystrophy (FECD), analyzed their segregation patterns families. Methods recruited 120 unrelated Caucasian subjects with FECD 100 controls. Available family members of probands were recruited. Genotyping single nucleotide polymorphism (SNP) rs613872 was performed using Sanger sequencing or real-time allelic discrimination assay. The trinucleotide repeat polymorphism, CTG18.1, genotyped a combination short tandem assay triplet primed PCR cytosine-thymine-guanine (CTG) length ≥40 classified as an expanded CTG18.1 allele. Association loci evaluated. Segregation 29 families examined. Results are linkage disequilibrium (r(2) = 0.65 cases 0.31 controls). Significant associations found (P 3.1 × 10(-17)), allele 6.5 10(-25)), haplotypes 5.9 10(-19)). odds ratio (OR) each copy G for estimated to be 9.5 (95% confidence interval [CI], 5.1-17.5). OR 32.3 CI, 13.4-77.6). CTG 18.1 cosegregated trait 52% (15/29) complete penetrance 10% (3/29) incomplete penetrance. Conclusions report, our knowledge, first independent replication conferring significant risk (>30-fold increase). cosegregates majority families, but we also document