2002 Fiscal Year Final Research Report Summary
Molecular genetics of hereditary ophthalmic diseases
| Project/Area Number |
12470364
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Osaka University |
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Principal Investigator |
OKADA Masaki Osaka University Graduate School of Medicine, Assistant professor, 医学系研究科, 助手 (90344457)
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| Co-Investigator(Kenkyū-buntansha) |
TANO Yasuo Osaka University Graduate School of Medicine, professor, 医学系研究科, 教授 (80093433)
MORIMURA Hiroyuki Osaka University Graduate School of Medicine, Assistant professor, 医学系研究科, 助手 (70314325)
NISHIDA Kohji Osaka University Graduate School of Medicine, Assistant professor, 医学系研究科, 助手 (40244610)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Corneal dystrophy / Stargardt disease / Retinitis pigmentosa / Candidate gene approach / SNP / Open angle glaucoma |
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| Research Abstract |
To evaluate photoreceptpr cell-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) gene mutations we investigated Japanese patients with Stargardt disease (STGD) and the correlation of these mutations to clinical phenotypes. We obtained genomic DNA from 10 unrelated Japanese patients with STGD and 96 unrelated Japanese patients with autosomal recessive retinitis pigmentosa (arRP). All 50 ABCA4 gene exons of the patients with STGD were screened for mutations by a combination of single-strand conformation polymorphism analysis and polymerase chain reaction (PCR) direct-sequencing techniques. By restriction enzyme digestion, primer extension analysis, and PCR direct sequencing techniques, the patients with arRP were screened for three segregated, presumably null ABCA4gene mutations observed in Japanese patients with STGD, We identified three novel, presumably null mutations of the ABCA4gene, IVS7-45_952delinsTCTGACC, IVS12+2T→G, and 1894delA. The Arg2149stop mutation that had been found in a white patient with STGD in a prior study was also found in a Japanese patient. Two arRP-affected siblings and two unrelated patients with STGD were found to be homozygous for the same IVS12+2T→G mutation, and three other arRP-affected sibhngs were carriers of the IVS12+2T→G mutation and/or the IVS7-45_952delinsTCTGACC mutation. These three sibhngs with arRP showed only atrophic degeneration in the macula early after the onset of the disease, and STGD had been diagnosed. We concluded that the ABGA4gene can cause panretinal degeneration that changes its clinical appearance from STGD to arRP over time.
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