Association and Familial Segregation of CTG18.1 Trinucleotide Repeat Expansion ofTCF4Gene in Fuchs' Endothelial Corneal Dystrophy

• DOI: 10.1167/iovs.13-12611
• Publication Date: 2013-11-20T02:37:06Z
• Authors: V. Vinod Mootha; Xin Gong; Hung-Chih Ku; Chao Xing
• Keywords: Linkage Disequilibrium; Penetrance; Sanger sequencing

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.We 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 cytosinethymine-guanine (CTG) length ‡40 classified as an expanded CTG18.1 allele.Association loci evaluated.Segregation 29 families examined.RESULTS.The are linkage disequilibrium (r 2 ¼ 0.65 cases 0.31 controls).Significant associations found (P 3.1 3 10 À17 ), allele 6.5 À25 haplotypes 5.9 À19 ).The odds ratio (OR) each copy G for estimated to be 9.5 (95% confidence interval [CI], 5.1-17.5).The OR 32.3 CI, 13.4-77.6).The CTG 18.1 cosegregated trait 52% (15/29) complete penetrance 10% (3/29) incomplete penetrance.CONCLUSIONS.We report, our knowledge, first independent replication conferring significant risk (>30-fold increase).The cosegregates majority families, but we also document penetrance.