肝豆状核变性ATP7B基因外显子突变研究  

Study on the Exon Mutation of ATP7B Gene with Wilson Disease

作　　者：张忠胜[1] 朱英武[1] 徐竹[1] 张艺凡[1] 刘琦[1] 方旭明[1] 刘太双[1] 楚兰[1] 

机构地区：[1]贵州省贵阳医学院附属医院神经科,550004

出　　处：《贵州医药》2008年第11期963-966,共4页Guizhou Medical Journal

摘　　要：目的研究Wilson病(WD)ATP7B基因突变的特点,探讨WD基因诊断的意义和方法,并分析WD患者基因型和临床表型之间的关系。方法应用PCR产物直接DNA测序法对18例WD患者及其21例亲属的第8、12、14号外显子进行检测,分析临床表型与ATP7B基因突变类型的关系。结果(1)3个外显子共发现7种类型突变,均为点突变,其中同义突变3种,错义突变4种;(2)Arg778Leu突变和Lys952Arg突变的患者与其无该点突变的患者比较,临床表现都未见明显差异。结论(1)产物DNA直接测序法可用于WD的早期诊断;ATP7B基因8号外显子778密码子是WD患者的高频突变位点;12号外显子952密码子可能是WD患者的高频突变位点;我们的实验未发现14号外显子基因突变;(2)Arg778Leu突变和Lys952Arg突变与临床表型在本研究中均未发现有相关性。Objective To determine the mutation characters of ATP7B gene and explore the importance of gene diagnosis for Wilson disease （WD） patients, and to analyze the correlation between genotype and phenotype 18 patients with 21 relatives. Methods Amplifying the exonS, exonl2 and exon14 of ATP7B gene by polymerase chain reaction （PCR）. PCR products were analyzed by direct DNA sequencing which were analyzed the correlation between genotype and phenotype. Results 7 various kinds of mutations which were all point mutations in the three exons were identified by DNA sequen- cing. Among them, including three same sense mutations and four miss sense mutations. Compared with the patients between the mutation group with Arg778Leu and the mutation group with Thr935Met, the clinical features were not found significant differences between genotype and pheno- type. Conclusion Gene diagnosis could be used for early identification of Wilson disease （WD） by using DNA direct sequence method to PCR products. Arg778Leu of exon8 was a hot point mutation of ATp7B gene, and Lys952Arg of exonl2 maybe also a hot point mutation of ATPTB gene in this study. Exonl4 mutation of ATP7B gene was not discovered in this experiment. The mutation groups with Arg778Leu and Lys952Arg show no significant relativity to clinical aspects of patients.

关 键 词：肝豆状核变性 外显子 基因突变 临床表型 

分 类 号：R329.23[医药卫生—人体解剖和组织胚胎学]