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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: To screen high-frequency mutation of hepatolenticular degeneration in Chinese. Methods: Exon 8 and exon 14 of 45 patients with Wilson’s disease in 39 Chinese families with Wilson’s disease were screened by PCR-SSCP. Sequence analysis (autoradiography) of those with abnormalities was performed, Cut again screening. Results: Exon8 was found to have three motile abnormalities and two of them were polymorphic. The sequence analysis of one patient with obvious abnormalities showed that: ①The sequence of patients found synonymous mutation C2250 → G, missense mutation G2273 → T Arg778Leu, caused Loss of function. Patients with both mutations coexist. ② The father of the patient had both C and G bases at 2250 and G and T bases existed at 2273. ③ found that patients with homozygous, his father is heterozygous, the mother for the normal sequence. According to the mutation of Arg778Leu, digestion was performed in all the patients. Two homozygotes accounted for 44% of the patients and 114 heterozygotes accounted for 244%. The positive rate of digestion was 28.8%. CONCLUSIONS: This result supports codon 7 of exon 8 as a high frequency mutation in Chinese Wilson’s disease. A similar phenomenon of loss of heterozygosity (LOH) appeared in this study, suggesting that LOH may occur in other genetic diseases besides tumors. Exon14 no abnormalities, and Europeans are obviously different.