单核苷酸多态性微阵列芯片在早期自然流产绒毛组织遗传学分析中的应用

Single nucleotide polymorphism-array in genetic analysis of chorionic villi from early spontaneous miscarriages

目的:探索单核苷酸多态性(SNP)微阵列技术在流产组织遗传学分析中的应用价值。方法:收集2013年10月至2016年6月浙江大学医学院附属妇产科医院不明原因早期自然流产的861例患者的绒毛组织,采用SNP芯片技术对流产绒毛组织的全基因组DNA拷贝数变异进行检测。结果:SNP芯片成功检测所有绒毛组织,成功率为100%。染色体异常检出率为51.10%(440/861),包括染色体非整倍体358份(41.58%),其分布于除1号染色体外所有染色体;三倍体21份(2.44%);单倍体1份(0.12%);单一位点缺失或重复37份(4.30%),其中25例缺失或重复片段小于10 Mb,对其中6例致病性不明确的病例进行夫妇芯片验证,结果显示4份为新发突变,2份遗传自夫妇一方;同时具有两位点缺失或重复23份(2.67%),对其中17份结合夫妇芯片及染色体核型、荧光原位杂交验证,发现新发突变6份,夫妇存在小片段平衡结构异常11份。结论:SNP微阵列芯片可对流产绒毛组织进行相对全面的遗传学分析,发现引起流产的各种遗传因素。

Objective：To assess the clinical application of single nucleotide polymorphism （SNP）-array in detecting abnormal chromosome karyotypes of chorionic villi from early spontaneous abortuses. Methods：A total of 861 chorionic villus samples from unexplained early spontaneous abortion were collected from Women＇s Hospital, Zhejiang University School of Medicine during October 2013 and June 2016, and SNP-array was performed to detect genome-wide DNA copy number variants. Results：All samples were successfully tested by SNP-array and 440 cases （51.10%） were found to have abnormal chromosome constitutions. Aneuploidy was identified in 358 （41.58%） cases, distributing in all chromosomes except chromosome 1. Triploidy and haploidy were found in 21 （2.44%） and one case （0.12%）, respectively. Thirty-seven cases （4.30%） were identified as single chromosomal segment deletion or duplication, 25 of which were less than 10 Mb in size. For 6 of 25 cases with unclear pathogenesis, family studies were carried out to identify origin of deletion or duplication, showing that 4 cases were de novo and 2 were inherited from one of the parents. Twenty-three cases （2.67%） showed two chromosomal deletion/duplication segments. Combining with karyotyping and fluorescence in situ hybridization, 6 cases were identified as de novo aberration and 11 carried small-size segmental balanced abnormality. Conclusion：SNP-array can provide a relatively comprehensive genetic analysis of chorionic villi and can detect various kinds of chromosome abnormalities in spontaneous miscarriages.