染色体单体型分析及突变检测在Wilson病临床诊断中的应用

目的建立染色体单体型分析法与突变检测相结合的Ｗｉｌｓｏｎ病（Ｗｉｌｓｏｎ＇ｓｄｉｓｅａｓｅ，ＷＤ）的基因诊断方法。方法以８个汉族ＷＤ家系为对象，用Ｄ１３Ｓ３１６、Ｄ１３Ｓ１３３和Ｄ１３Ｓ３１４３个［ＣＡ］ｎ重复遗传标记构建染色体单体型，进行ＷＤ家系内的诊断研究；对先证者的致病突变已明确的５个家系，同时用ＰＣＲ－ＳＳＣＰ检测法检测突变以完善诊断。结果找到了１例无症状期ＷＤ患者，５例杂合子。结论通过分析Ｄ１３Ｓ３１６、Ｄ１３Ｓ１３３、Ｄ１３Ｓ３１４构成的染色体单体型，基本可为先证者同胞兄妹明确诊断；对致病突变已确定的家系，突变检测能为诊断提供直接而肯定的依据。两种方法的联合使用可为诊断提供更多的依据

Clinical Application of Chromosome Haplotype Analysis and Mutation Analysis to the Diagnosis of Wilson's Disease

Objective To set up the method of gene diagnosis of Wilson's disease by chromosome haplotype analysis and mutation detection.Methods This study selected 3 (CA)n repeat genetic markers, D13S316,D13S133 and D13S314 to construct the chromosome haplotype within 8 Han WD families. PCR SSCP was used to reconfirm the diagnosis of the siblings of the probands in the families where in the disease causing mutation had been detected.Results One asymptomatic WD patient and 5 heterozygotes were detected. Conclusion In the WD families, the analysis of chromosome haplotype helps to make the diagnosis of siblings of the probands; for the WD families in which the disease causing mutation has been ascertained, mutation analysis can provide direct and definite evidence for diagnosis. The combination of these two methods can provide more evidences for diagnosis.