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Molecular Biological Diagnosis of Xeroderma Pigmentosum group A and Clinical Characteristics

A组色素性干皮病的分子生物学诊断及临床特征

基本信息

批准号：
05807071
负责人：
MATSUYOSHI Norihisa
金额：
$ 1.09万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05807071/
关键词：
Xeroderma Pigmentosum Mutation PCR-RFLP Gene Diagnosis Founder Effect XPAL遺伝子 RFLP

项目摘要

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.

对46例着色性干皮病（XP）A组患者进行XPA基因突变检测，其中41例（89%）患者的内含子3发生剪接突变，经限制性内切酶AlwN I的PCR-RFLP证实（Alw NI -/-），具有这种剪接突变的人显示皮肤癌的早期发病（大多数病例在10岁之前）和严重的神经系统症状。2例患者为内含子3剪接突变（Alw NI +/-）和外显子6第228位密码子无义突变的复合杂合子，经PCR-RFLP证实为Hph I（Hph I +/-）。1例患者第3外显子第116位密码子突变（Mse I +/-），经限制性内切酶Mse I限制性片段长度多态性（PCR-RFLP）证实为第3内含子杂合剪接突变（Alw N I +/-），1例患者第6外显子第228位密码子纯合突变（Hph I -/-），24岁时发生皮肤癌并伴有精神神经系统症状。提示不同基因型有不同的临床特征。1例患者在杂合子状态下有内含子3的剪接突变（Alw N I +/-），而没有任何其他已知的突变。用PCR-SSCP方法检测XPA基因突变情况，发现该患者存在XPA基因第5外显子最后一个密码子的杂合突变。在突尼斯的XPA患者中，7名患者中有6名显示Hph I -/-基因型，尽管那里的阳光很强，但他们在20岁左右患上了皮肤癌。这与日本Hph I -/-患者表现出较轻临床特征的数据一致。结果表明，PCR-RFLP和PCR-SSCP在XP诊断中是有用的。其临床特征与突变位点密切相关。观察到XPA基因两种突变的奠基者效应。