摘要：
目的 应用多重连接依赖式探针扩增(MLPA)技术分析胚胎停育及自然流产患者绒毛组织中常见的染色体非整倍体异常,为复发性自然流产、胚胎停育提供遗传病的病因资料.方法采用临床回顾性研究,对2013年11月至2016年10月在深圳市妇幼保健院就诊的7 036例胚胎停育或自然流产患者的绒毛或胎儿组织标本进行分析,所有标本均用树脂和蛋白酶K提取基因组DNA,应用MLPA技术检测染色体非整倍体异常,并用SPSS 17.0进行描述性和频数统计分析.结果7 036份流产组织标本中,染色体非整倍体异常共2 984份,占42.41%.其中异常比例最高的前5位依次为:16三体(826份)11.74%、X0单体(401份)5.70%、22三体(247份)3.51%、13三体(149份)2.12%、21三体(144份)2.05%,19号和17号染色体非整倍体异常最少见,分别有1份和3份,而1号染色体尚未发现非整倍体异常;部分三体和部分单体共161份(2.28%);单体中除X0比例最高外,21单体较常见(17份,0.24%);双三体共56份(0.80%);三三体2份(0.03%);性染色体三体13份(0.18%);X0合并常染色体三体5份(0.07%);臂间不平衡易位15份(0.21%);非同源染色体间易位20份(0.28%).结论 三体和单体占绒毛染色体数目异常的绝大部分(90%以上),也是胚胎停育和自然流产的主要原因.同时利用MLPA可以全面、经济、快速地筛查出绒毛染色体非整倍体异常(即大片段的缺失或重复),从而进一步发现夫妇中可能存在的平衡易位携带者,为再次妊娠提供有价值的遗传信息.%Objective To investigate chromosomal aneuploidy of chorionic villior tissue from embryo arrestor spontaneous miscarriage by the method of multiplex ligation-dependent probe amplification(MLPA), and to provide genetic etiology data for recurrent spontaneous abortion(RSA) and embryo arrest.Methods The clinical retrospective analysis was used during November 2013 to October 2016 in Shenzhen Maternity and Child Healthcare Hospital.The genomic DNA of 7 036 chorionic villi or tissue samples from embryo arrestor pregnancy loss were extracted by resin and Proteinase K, following detected by multiplex ligation-dependent probe amplification, and then analyzed by descriptive and frequency statistic using SPSS17.0 software.Results Totally 2 984 samples (42.41%) with chromosomal aneuploidy were detected, of which, the top five were trisomy 16(826)11.74%, monosomy X (Turner,401)5.70%, trisomy 22(247)3.51%, trisomy 13(149)2.12% and trisomy 21(144)2.05%.Aneuploidy 19 or 17 were rare,just 1 and 3 cases respectively.The aneuploidy of chromosome 1 was not discovered yet.There were 161 samples (2.28%) for segmental deletion and/or duplication cases.Besides of the monosomy X(Turner,401), monsomy 21 was also high frequency(17,0.24%).In addition, 56 samples(0.80%)were double trisomic,while 2 samples(0.03%)were tris-trisomy.Thirteen samples(0.18%)were heterosome trisomy,and five samples(0.07%)were Turner combined trisomy.Fifteen samples(0.21%) were unbalanced translocation of the arm,while 20 samples(0.28%) were nonhomologous chromosome translocation.Conclusions Trisome and monosome were the majority of chromosome abnormality (above 90%), as well as the main cause of spontaneous miscarriage.Meanwhile the chromosome aneuploidy (including segment deletion or duplication) could be screened by MLPA quickly, thoroughly and efficiently, further more discover the carrier of balanced translocation in couples and provide valuable genetic information for next pregnancy.
