308例高危妊娠产前诊断CMA技术发现不明确拷贝数变异的结果分析

摘要

Objective:To explore the application of chromosomal microarray analysis (CMA) in the patients with high-risk pregnancy.Methods:A total of 308 patients with high-risk pregnant who were admitted to Peking Union Medical College Hospital for prenatal diagnosis,and detected by CMA and karyotype analysis from Jan.1 2014,to Jun.1 2017 were recruited in this study.The CMA results were analyzed and compared with the karyotyping,and the composition and the characteristics of the various clinical unambiguous significances (VOUS) were also analyzed.Results:A large proportion (88.0％) of the patients was abnormal in fetal structure or soft marker,and had fetal growth restriction or fetal edema.Whole genome detection did not reveal a clear chromosome copy number change (CNV) or clear polymorphic changes in 217 patients (70.5％),and 44 patients (14.3％) were identified with pathological CNV.Among them,21 patients had chromosomal aneuploidy abnormalities,6 patients abnormal sex chromosome number,17 patients chromosome pathogenic CNV.In addition,47 patients had various clinical unambiguous significances of CNV results (15.3％).Among them,23 patients were likely benign,and 21 patients were truly clinical unambiguous significance.There was one patient with loss of heterozygous (LOH) and three patients with likely pathogenic.This study also further analyzed the distribution of fragment size and the type of interpretation based on VOUS in the patients.The positive rate of chromosome abnormality by CMA was 14.2％,compared with 10.7％ of the positive rate of karyotyping,and the positive rate increased by 3.5％.Conclusions:The diagnostic efficiency of genome-wide chromosome microarray chip for fetal structural abnormality is higher than that of karyotype analysis.However,there was also difficulty in the proper genetic counseling for VOUS.At present,the proportion of domestic prenatal diagnosis of clinical unambiguous significance is high,which is related to the low level of local database,lack of domestic specific microarray results interpretation criteria.%目的 探讨染色体微阵列分析(CMA)在高危妊娠产前诊断中的应用,观察其中临床意义不明的染色体拷贝数变异(VOUS)结果构成及相关特性,分析将该技术广泛应用于产前染色体病诊断临床检测的可行性. 方法 选择2014年1月1日至2017年6月1日期间于北京协和医院就诊并接受产前诊断,同时进行CMA及核型分析检测的孕妇308例,对其CMA检测的结果进行分类分析并与核型分析相比较,分析其中不明确意义结果的构成以及相关特性. 结果 所有人组病例中88,0％为各种胎儿结构异常、软指标异常、胎儿生长受限及胎儿水肿.全基因组检测未发现明确染色体拷贝数改变(CNV)或明确多态性改变的病例217例,占70.5％;发现明确致病性染色体数目或片段异常共44例,占14.3％.其中发现染色体非整倍体异常21例,性染色体数目异常6例,染色体致病性CNV结果17例.此外发现不明意义的CNV诊断结果47例,占总病例数的15.3％.其中致病性判读为偏良性的23例,临床意义不明为21例,含符合报告标准的杂合性缺失(IOH)1例,偏致病性的3例.进一步分析各种VOUS病例的片段大小分布及判渎依据类型.与核型分析的异常阳性率10.7％比较,全基因染色体芯片诊断明确致病性的染色体异常阳性率为14.2％,诊断阳性率提升3.5％. 结论 全基因组染色体芯片对于超声发现胎儿结构异常的遗传诊断能力较核型分析有较大的提升,但同时也会有VOUS病例增加遗传咨询的难度.目前国内产前诊断VOUS结果的比例较高,这与本地化数据库不完善,缺乏国内具体的芯片结果判读标准等有关.