摘要
目的：筛选中国人肝豆状核变性的高频突变点。方法：对中国人肝豆状核变性３９个家系４５个患者的８号、１４号外显子进行ＰＣＲＳＳＣＰ筛选，对有异常者进行序列分析（放射自显影），并通过该突变点的酶切再次筛选。结果：Ｅｘｏｎ８发现有３个泳动异常，两个为多态现象，对１例明显异常者序列分析表明：①患者的序列发现同义突变Ｃ２２５０→Ｇ，错义突变Ｇ２２７３→Ｔ发生Ａｒｇ７７８Ｌｅｕ，引起功能缺失。患者上述两个突变同时存在。②患者父亲在２２５０位点Ｃ及Ｇ碱基同时存在，在２２７３位点Ｇ及Ｔ碱基同时存在。③发现患者为纯合子，其父为杂合子，母亲为正常序列。针对Ａｒｇ７７８Ｌｅｕ突变在所有病人中进行酶切，发现２例纯合子占病人总数４４％，１１例杂合子占２４４％。酶切的阳性率为２８．８％。结论：本结果支持８号外显子７７８密码子作为中国人肝豆状核变性的高频突变点。本研究中出现类似杂合性丢失（ＬＯＨ）现象，提示ＬＯＨ现象可能发生在除肿瘤之外的其他遗传疾病中。Ｅｘｏｎ１４未见异常，与欧洲人明显不同。
Objective:Screen for high frequency of gene mutation in Chinese patients with Wilson disease.Methods:PCRSSCP was used to screen in exon 8 and 14 with 45 Wilson disease patients in 39 Chinese families and 10 were normal controls; nucleotide sequence analysis by autoradiograph and restriction enzyme digest to the mutate point were carried out.Results:3 mobility shifts with exon 8 were found, but only one mobility shift was affirmed by families analysis of SSCP. There was one missense mutation Arg778 Leu and one same sense mutation C2250→G at the patient. Arg778 Leu mutation point were digested by restriction enzyme Msp Ⅰ at all patients; homozygous patients was 4.4%, heterozygous patients was 24.4%. The authors had not found any abnormal with exon 14.Conclusions:The result supports the viewpoint that the high frequency of mutation in Chinese patients with Wilson disease is 778 codon of exon 8. No abnormal was found in exon 14, it is very different with Europe patients. Meantime, the authors found a loss of heterozygosity (LOH) in a family with Wilson disease. This suggested that LOH might happen in other hereditary disease besides tumor and cancer.
出处
《中山医科大学学报》
CSCD
1998年第1期14-17,26,共5页
Academic Journal of Sun Yat-sen University of Medical Sciences
基金
国家自然科学基金
广东省自然科学基金
关键词
肝豆状核变性
基因突变
外显子
hepatolenticular degeneration/genetics
gene mutation
exons
