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REP-1 gene mutations in Japanese patients with choroideremia
K Fujiki1, Y Hotta, M Hayakawa
1Department of Ophthalmology, Juntendo University School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan,
Insights
Researchers identified 15 distinct REP-1 gene mutations in 18 Japanese families with choroideremia (CHM). These REP-1 gene defects cause CHM, with unique mutations suggesting independent occurrences in Japanese patients.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- Choroideremia (CHM) is an X-linked progressive retinal dystrophy.
- The REP-1 gene is identified as the causative gene for CHM.
- Previous studies identified REP-1 gene mutations in CHM patients.
Purpose of the Study:
- To conduct an extensive analysis of the REP-1 gene in Japanese patients with choroideremia.
- To identify novel mutations and characterize REP-1 gene defects in a Japanese cohort.
Main Methods:
- Screening of exons 1-15 of the REP-1 gene using single-strand conformation polymorphism in 26 CHM patients.
- Direct sequencing of DNA fragments with suspected variations.
- Examination of 5 unaffected females for carrier status.
Main Results:
- Fifteen distinct REP-1 gene mutations were detected in 18 out of 22 families.
- One previously reported mutation was identified.
- Carrier status was confirmed in four unaffected females.
Conclusions:
- REP-1 gene defects are confirmed as the cause of CHM in Japanese patients.
- The identified mutations in Japanese patients differ from those reported in other populations, except for two specific mutations (R267X and 1313delTC).
- These findings suggest independent mutation events in the Japanese CHM patient cohort.
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.