摘要:
目的 探讨细菌人工染色体标记-磁珠分离法(BoBs)分子诊断技术在早期自然流产遗传学分析中的应用,并评价其临床应用价值.方法 收集2014年7月至2015年1月间在中国医学科学院北京协和医学院北京协和医院就诊、临床确诊为早期自然流产的患者161例,在行清宫术时留取绒毛组织进行BoBs检测,同时进行传统染色体G显带核型分析,比较两种检测方法的一致性,并评价BoBs分子诊断技术的应用价值.结果 (1)161例早期自然流产患者中,BoBs检测均成功,成功率为100.0%(161/161);染色体G显带核型分析131例成功,失败30例,成功率为81.4%(131/161).两种检测方法成功率比较,差异有统计学意义(x2=33.082,P<0.01).(2)BoBs检测耗时(2.7±0.6)d,染色体G显带核型分析成功患者耗时(22.5±1.9)d,两者比较,差异有统计学意义(t=123.315,P<0.01).(3)161例行BoBs检测的患者中,染色体正常76例(47.2%,76/161);染色体异常85例(52.8%,85/161),其中染色体数目异常79例、其他异常(包括染色体片段缺失、嵌合等)6例.131例染色体G显带核型分析成功的患者中,染色体正常52例(39.7%,52/131);染色体异常79例(60.3%,79/131),其中染色体数目异常62例、其他异常17例.BoBs检测异常染色体的检出率低于染色体G显带核型分析,但两者比较,差异无统计学意义(x2=1.655,P=0.198).对于30例染色体G显带核型分析失败的早期自然流产患者,BoBs检测均成功,其中染色体正常8例,染色体异常22例,包括染色体数目异常18例、其他异常4例.(4)131例有染色体G显带核型分析结果的患者中,BoBs检测结果与染色体G显带核型分析结果一致者108例(包括染色体数目正常51例、染色体数目异常57例),不一致者23例,一致率为82.4%(108/131).131例有染色体G显带核型分析结果的患者中,以染色体G显带核型分析结果作为标准,BoBs检测方法对于检测染色体异常的准确率为82.4%(108/131),敏感度为72.2%(57/79),特异度为98.1%(51/52);对于染色体G显带核型分析结果为染色体正常及染色体数目异常的114例患者,BoBs检测方法对于检测染色体数目的准确率为94.7%(108/114),敏感度为91.9%(57/62),特异度为98.1%(51/52).结论 BoBs分子诊断技术与传统染色体G显带核型分析技术相比,是1种快速、成功率高、检测准确率高的染色体检测方法,可以作为早期自然流产遗传学分析的方法之一.%Objective To investigate the value of bacterial artificial chromosome-on-beads(BoBs) technology in the genetic analysis of early missed abortion chorionic villi. Methods Early missed abortion chorionic villi were detected with both conventional karyotyping method and BoBs technology in Peking Union Medical Hospital from July 2014 to March 2015. Compared the results of BoBs with conventional karyotyping analysis to evaluate the sensitivity, specificity and accuracy of this new method. Results (1) A total of 161 samples were tested successfully in the technology of BoBs, 131 samples were tested successfully in the method of conventional karyotyping.(2)All of the cases obtained from BoBs results in(2.7 ± 0.6) days and obtained from conventional karyotyping results in (22.5 ± 1.9) days. There was significant statistical difference between the two groups(t=123.315, P<0.01).(3)Out of 161 cases tested in BoBs, 85(52.8%, 85/161)cases had the abnormal chromosomes, including 79 cases chromosome number abnormality, 4 cases were chromosome segment deletion, 2 cases mosaic. Out of 131 cases tested successfully in conventional karyotyping, 79(60.3%, 79/131)cases had the abnormal chromosomes including 62 cases chromosome number abnormality, 17 cases other chromosome number abnormality, and the rate of chromosome abnormality between two methods was no significant differences(P=0.198).(4)Conventional karyotyping results were served as the gold standard, the accuracy of BoBs for abnormal chromosomes was 82.4%(108/131), analysed the normal chromosomes (52 cases) and chromosome number abnormality (62 cases)tested in conventional karyotyping, the accuracy of BoBs for chromosome number abnormality was 94.7%(108/114). Conclusion BoBs is a rapid reliable and easily operated method to test early missed abortion chorionic villi chromosomal abnormalities.