Corneal dystrophies in Japan

J Hum Genet. 2001;46(8):431-5. doi: 10.1007/s100380170041.

Abstract

Recent advances in molecular genetics have increased our understanding of the role of genes. Four autosomal dominant corneal dystrophies (CDs); granular CD (GCD), Avellino CD (ACD), lattice CD (LCD), and Reis-Bücklers CD (RBCD) were mapped to the long arm of chromosome 5 (5q31). These four diseases were shown, in a Caucasian series, to result from different missense mutations in the TGFBI (BIGH3, keratoepithelin) gene. The same mutations were also detected in Japanese patients, from a different ethnic background. Gelatinous drop-like corneal dystrophy (GDLD), on the other hand, which was found in Japanese patients in 1914, is a rare autosomal recessive disorder characterized by corneal amyloidosis. Parents of the patients had a markedly higher frequency of consanguineous marriages than the general population. The gene responsible for GDLD, the membrane component, chromosome 1, surface marker 1 (M1S1) gene was mapped to the short arm of chromosome 1(1p). Four deleterious mutations in this gene were detected in Japanese patients. We review here additional studies on mutations of the TGFBI and M1S1 genes found in Japanese patients. In the TGFBI gene, nine different mutations were detected 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 were ACD patients with the R124H mutation. New mutations responsible for LCD were detected in the TGFBI gene of patients with LCD, in addition to the P501T mutation in LCD type IIIA found earlier. These studies showed a clear genotype/phenotype correlation associated with the TGFBI gene. In the M1S1 gene, the Q118X mutation was the most common alteration, and a founder mutation in Japanese GDLD patients, as previously reported. Ninety-two percent of the mutated alleles were the Q118X.

Publication types

  • Review

MeSH terms

  • Corneal Dystrophies, Hereditary / classification
  • Corneal Dystrophies, Hereditary / genetics*
  • Corneal Dystrophies, Hereditary / pathology
  • DNA Mutational Analysis
  • Extracellular Matrix Proteins*
  • Genetic Predisposition to Disease / ethnology
  • Humans
  • Japan / epidemiology
  • Molecular Biology
  • Mutation, Missense / genetics*
  • Neoplasm Proteins / genetics*
  • Polymerase Chain Reaction
  • Transforming Growth Factor beta / genetics*

Substances

  • Extracellular Matrix Proteins
  • Neoplasm Proteins
  • Transforming Growth Factor beta
  • betaIG-H3 protein