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目的 探讨Wilson病(WD)基因突变类型与临床表型的关系。方法 应用聚合酶链反应-单链构象多态分析(PCR-SSCP)和DNA测序方法,对84例WD患者进行WD基因全长21个外显子的突变检测,结合统计学方法,着重分析并探讨中国人WD基因突变热点Arg778Leu基因型与临床表型的关系。结果 18例患者检出Arg778Leu纯合突变。29例患者在一条染色体上检出Arg778Leu杂合错义突变,其中,在另一条染色体上,3例检出移码突变;15例突变未明;余11例检出其他错义突变。就理论而言,与错义突变相比,移码突变可导致更严重的功能缺陷及表型,不能与错义突变混合进行统计学分析,另15例患者因有一条染色体突变未明亦被排除在外。因此,相对Arg778Leu纯合错义突变进行统计学分析时,只能选择11例发生复合错义突变的患者做为Arg778Leu杂合突变病例组。经统计学分析,携带Arg778Leu纯合突变的患者和携带Arg778Leu杂合突变的患者,其起病年龄、血清铜蓝蛋白水平及临床类型均差异有显著意义,P值小于0.05或0.001。结论 Arg778Leu突变不是一种温和的突变,它可导致患者症状出现较早并较严重。
Objective To explore the relationship between the type of Wilson’s disease (WD) mutation and clinical phenotype. Methods Eighty-four cases of WD patients were detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The mutations of 21 exons of WD gene were detected by statistical methods. To investigate the relationship between the genotypes of Arg778Leu and the clinical phenotypes of Chinese WD gene mutation hot spots. Results 18 patients were detected Arg778Leu homozygous mutation. Among the 29 patients, a heterozygous missense mutation of Arg778Leu was detected on one chromosome, of which 3 showed a frameshift mutation on the other chromosome, 15 were unknown, and 11 missense mutations were detected on the other 11. In theory, frameshift mutations can lead to more severe functional defects and phenotypes than missense mutations, and can not be mixed with missense mutations for statistical analysis, and the other 15 patients were excluded because of a chromosomal mutation outer. Therefore, relative to Arg778Leu homozygous missense mutation statistical analysis, only 11 patients with complex missense mutations were selected as Arg778Leu heterozygous mutation group. Statistically, patients with Arg778Leu homozygous mutation and patients with heterozygous mutation of Arg778Leu had significant difference in onset age, serum ceruloplasmin level and clinical type, P value was less than 0.05 or 0.001. Conclusion Arg778Leu mutation is not a mild mutation, which can lead to earlier and more serious symptoms in patients.