染色体单体型分析及突变检测在Wilson病临床诊断中的应用

• 作 者: 施小六 凌奇荷 夏家辉 伍汉文
• 机 构: 湖南医科大学第二临床学院
• 出 处: 中华医学遗传学杂志
• 发表日期: 1999年01期
• 关键词: Wilson病 突变检测 单体型分析 基因诊断 先证者 无症状期 家系图 临床诊断 遗传标记 基因突变

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

Objective To establish a genetic diagnosis method of Wilson’s disease (WD) combined with chromosomal haplotype analysis and mutation detection. Methods 8 Han Chinese pedigrees were used as the object to construct chromosomal haplotypes with D13S316, D13S133 and D13S314 [CA] n repeat genetic markers to make a diagnostic study in the WD pedigree. The pathogenic mutation of probands was identified as 5 A pedigree, at the same time PCR-SSCP detection of mutations to improve the diagnosis. Results One patient with asymptomatic WD was found and five patients were heterozygous. Conclusion The haplotypes of D13S316, D13S133 and D13S314 can be diagnosed by sibling siblings of probands. The mutation detection can provide direct and affirmative basis for the diagnosis of pedigrees with pathogenic mutation. The combination of the two methods can provide more evidence for diagnosis