REP-1 gene mutations in Japanese patients with choroideremia

Graefes Arch Clin Exp Ophthalmol. 1999 Sep;237(9):735-40. doi: 10.1007/s004170050305.

Abstract

Background: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan.

Methods: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1-15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced.

Results: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele.

Conclusions: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alkyl and Aryl Transferases*
  • Asian People / genetics*
  • Base Sequence
  • Carrier Proteins / genetics*
  • Choroideremia / ethnology*
  • Choroideremia / genetics*
  • Female
  • Humans
  • Japan
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • Polymorphism, Single-Stranded Conformational
  • Reference Values
  • rab GTP-Binding Proteins*

Substances

  • Adaptor Proteins, Signal Transducing
  • CHM protein, human
  • Carrier Proteins
  • Alkyl and Aryl Transferases
  • rab GTP-Binding Proteins