Corneal dystrophies in Japan

Recent advances in molecular genetics have increased our understanding of t he role of genes. Four autosomal dominant corneal dystrophies (CDs); granul ar CD (GCD), Avellino CD (ACD), lattice CD (LCD), and Reis-Bucklers CD (RBC D) were mapped to the long arm of chromosome 5 (5q31). These four diseases were shown, in a Caucasian series, to result from different missense mutati ons in the TGFBI (BIGH3, keratoepithelin) gene. The same mutations were als o detected in Japanese patients, from a different ethnic background. Gelati nous drop-like corneal dystrophy (GDLD), on the other hand, which was found in Japanese patients in 1914, is a rare autosomal recessive disorder chara cterized by corneal amyloidosis. Parents of the patients had a markedly hig her frequency of consanguineous marriages than the general population. The gene responsible for GDLD, the membrane component, chromosome 1, surface ma rker 1 (M1S1) gene was mapped to the short arm of chromosome 1(lp). Four de leterious mutations in this gene were detected in Japanese patients. We rev iew here additional studies on mutations of the TGFBI and M1S1 genes found in Japanese patients. In the TGFBI gene, nine different mutations were dete cted in Japanese patients with GCD, ACD, LCD, or RBCD. The codons R124 and R555 of the TGFBI gene were hotspots in Japanese patients, of whom many wer e ACD patients with the R124H mutation. New mutations responsible for LCD w ere detected in the TGFBI gene of patients with LCD, in addition to the P50 1T mutation in LCD type IIIA found earlier. These studies showed a clear ge notype/phenotype correlation associated with the TGFBI gene. In the M1S1 ge ne, the Q118X mutation was the most common alteration, and a founder mutati on in Japanese GDLD patients, as previously reported. Ninety-two percent of the mutated alleles were the Q118X.