论文部分内容阅读
目的通过产前BAC-on-Beads技术对胎儿性染色体非整倍体和性染色体微缺失的检测,结合胎儿染色体核型分析和胎儿染色体全基因组微阵列分析(chromosomal microarray analysis,CMA)检测,以探讨Bo Bs技术用于检测胎儿性染色体非整倍体和微缺失/微重复检测的可行性。方法将2016年4月-2017年6月采集到的1576例具有产前诊断指征的单胎孕妇羊水,同时行产前Bo Bs与传统羊水染色体G显带核型分析,结合CMA验证并比较染色体异常的检测结果。结果在1576例羊水样本中,产前Bo Bs技术共检测出性染色体非整倍体异常14例:其中X探针检测区扩增异常减少2例;X探针检测区扩增异常增加7例;Y探针检测区扩增异常增多2例,X/Y探针检测区扩增异常增多1例;传统染色体核型结果为:1例45,XO;2例47,XXX;4例47,XXY;4例47,XYY;3例不同比例的性染色体嵌合体(嵌合比例均>20%),与Bo Bs检测提示结果均一致。产前Bo Bs检出11例性染色体的微缺失/微重复分别是:3例Yq11的缺失,4例Xp22的缺失;1例Xp22.33q28大片段的重复/缺失;经CMA验证:3例Yq11.23区段380Kb、395Kb、928.8Kb缺失;3例Xp22.31区段1.68Mb、1.5Mb、1.68Mb缺失;1例Xp22.33~p22.2片段12.8Mb缺失;1例Xp22.33~q28大片段的7.7Mb缺失、33.5Mb和106.4Mb的重复,3例拒绝验证。但只有2例Bo Bs检测染色体核型分析能辨析。结论产前Bobs技术可以准确检测出性染色体非整倍体异常,包括嵌合比例>20%的染色体核型;核型分析只能检测出性染色体>10Mb缺失/重复,而产前Bo Bs结合CMA验证可以准确检测出性染色体微缺失/微重复,且能较全面的检测胎儿性染色体异常,预防出生缺陷。
OBJECTIVE: To detect fetal chromosomal aneuploidy and sex chromosome microdeletion by prenatal BAC-on-Beads technique, combined with fetal karyotype analysis and fetal chromosomal microarray analysis (CMA) To explore the feasibility of using Bo Bs technique to detect fetal chromosomal aneuploidy and microdeletion / micro-repeat detection. Methods A total of 1576 pregnant women with single prenatal diagnosis of amniotic fluid collected from April 2016 to June 2017 were enrolled in this study. Prenatal Bo Bs and conventional amniotic fluid G banding karyotype analysis were combined with CMA to verify and compare Chromosome abnormalities test results. Results In 1576 cases of amniotic fluid samples, 14 cases of sex chromosome aneuploidy were detected by prenatal Bo Bs technique: 2 cases were abnormally reduced in X probe detection area, 7 cases were abnormally amplified in X probe detection area ; 2 cases of abnormal amplification of Y probe detection area, 1 case of abnormal amplification of X / Y probe detection area; 1 case of 45, XO; 2 cases of 47, XXX; 4 cases of 47, XXY; 4 cases of 47, XYY; 3 cases of sex chromosome chimeras with different ratios (> 20% of the chimerism), which were consistent with the results of Bo Bs test. Prenatal Bo Bs detected 11 cases of chromosomal microdeletions / micro-repeats were: 3 cases of Yq11 deletion, 4 cases of Xp22 deletion; 1 cases of Xp22.33q28 large fragment of the duplication / deletion; CMA verification: 3 cases of Yq11 .3 segments of 380Kb, 395Kb, 928.8Kb deletion; 3 cases of Xp22.31 segment 1.68Mb, 1.5Mb, 1.68Mb missing; 1 cases of Xp22.33 ~ p22.2 fragment 12.8Mb deletion; 1 case of Xp22.33 ~ q28 7.7Mb deletion of large fragments, 33.5Mb and 106.4Mb duplications, and 3 rejected validation. However, only 2 cases of Bo Bs detection of chromosome karyotype analysis can distinguish. Conclusions Antecedent Bobs technique can detect abnormalities of sex chromosome aneuploidy accurately, including chromosome karyotypes with chimerism> 20%. Karyotype analysis can only detect> 10Mb deletion / duplication of sex chromosomes while prenatal Bo Bs binding CMA verification can accurately detect the sex chromosome microdeletion / micro-duplication, and can more comprehensive detection of fetal chromosomal abnormalities, birth defects.