Six different mutations of TCFBI (beta ig-h3, keratoepithelin) gene found in Japanese corneal dystrophies

Purpose. To investigate mutations of the human transforming growth factor b eta-induced gene (TGFBI), transforming growth factor-beta-induced gene prod uct (beta ig-h3, keratoepithelin), in Japanese patients with Avellino corne al dystrophy (ACD), lattice corneal dystrophy (LCD), granular corneal dystr ophy (GCD), and Reis-Bucklers corneal dystrophy (RBCD). Methods. Genomic DN A was extracted from the peripheral blood of 75 patients and 7 unaffected r elatives from 60 families with ACD, 34 patients and 8 unaffected relatives from 21 families with LCD, 4 patients and 4 unaffected relatives from 4 fam ilies with GCD, and 4 patients and an unaffected relative from 3 families w ith RBCD. Fifty normal volunteers served as controls. Exons 4. 11. and 12 o f the TGFBI gene were amplified by polymerase chain reaction and were direc tly sequenced. Results. Six different heterozygous missense mutations were detected in codons R124, L518, L527. and R555 of the TCFBI gene in the 117 patients: from 88 families. A R124H mutation was detected in the patients w ith ACD. A R124C mutation was detected in the patients with LCD type 1 (LCD 1), L518P was in atypical LCD1, and L527R in LCD with opacities deep in str oma. A R555W mutation was: detected in the patients with GCD. A R555Q mutat ion was detected in the patients with RBCD. Conclusions. We conclude that c odons R124 and R555 of the TGFBI gene are also hot spots in Japanese patien ts with ACD, LCD, GCD, and RBCD. Many Japanese patients with CD had ACD wit h R124H mutation. GCD with R555W mutation was rare.