1994 Fiscal Year Final Research Report Summary
Molecular Biological Diagnosis of Xeroderma Pigmentosum group A and Clinical Characteristics
| Project/Area Number |
05807071
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
MATSUYOSHI Norihisa Kyoto Univ.Faculty of Medicine Instructor, 医学部, 助手 (10263071)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Toshihiro Kyoto Univ.Faculty of Medicine Instructor, 医学部, 助手 (50188314)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Xeroderma Pigmentosum / Mutation / PCR-RFLP / Gene Diagnosis / Founder Effect |
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| Research Abstract |
The gene alterations of XPA gene were identified on 46 patients belonging to xeroderma pigmentosu (XP) group A.Among those, 41 patients (89%) had splicling mutation in intron 3 which could be confirmed by PCR-RFLP using restriction enzyme, AlwN I (Alw NI -/-) , Those having this splicing mutation revealed early onset of skin cancer (most cases before the age of 10) and severe neurological symptoms. 2 patients were identified to be compound heterozygote of splicing mutation of intron 3 (Alw NI +/-) and nonsense mutation of codon 228 in exon 6 which could be confrmed by PCR-RELP using Hph I (Hph I +/-) . One patient had a mutation in codon 116 in exon 3 which could be confirmed by the PCR-RFLP using restriction enzyme Mse I at the heterozygous state (Mse I +/-) with heterozygous splicing mutation of intron 3 (Alw N I +/-) .One patient having homozygous mutation at codon 228 in exon 6 (Hph I -/-) developed skin cancer at the age of 24 and mind neurological sysmptoms. It implies different genotype reveals different clinical features. One patient had a splicing mutation of intron 3 at the heterozygous state (Alw N I +/-) without any other kown mutation. The presense of mutation in XPA gene was screened by PCR-SSCP and it was found that this patient had a mutation at the last codon of exon 5 in the heterozygous state. In Tunisian XPA patients 6 out of 7 patients revealed Hph I -/- genotype and they developed skin cancer around the age of 20 despite atronger Sun light there. This is consistent with the data in which the Japanese Hph I -/- patient showed milder clinical features. From our results the usefulness of PCR-RFLP and PCR-SSCP in the diagnosis of XP was shown. The clinical chracteristics appear to be closely related to the site of mutation. Founder effect of two types of muation of XPA gene was obserevd.
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