【摘要】 目的探讨胎儿游离无创基因产前检测技术(NIPT)联合染色体核心分析和细菌人工染色体微珠技术分析等可接受的多平台技术,建立胎儿唐氏综合征(DS)等染色体异常及染色体微缺失/微重复综合征的检出模式,评价多平台联合进行产前诊断对降低出生缺陷的临床应用效果。方法 2016年1月至2017年4月在我院遗传咨询门诊就诊,接受NIPT检测孕妇10 735例和具有产前诊断指征的孕妇4145例;NIPT提示信号异常的病例和具有产前诊断指征的病例接受介入性羊水穿刺,进行羊水染色体核型分析和或产前BoBs检测,对胎儿DS综合征等染色体非整倍体和各种染色体缺失/重复综合征进行确诊。结果在10 735例NIPT检测中,提示信号异常结果115例,检测异常率为1.07%(115/10 735)。高龄组异常检出率为1.55%(58/3742),高危组异常检出率为1.48%(36/2437),其它组异常检出率为0.46%(21/4556)。经NIPT检测阳性后经核型分析确诊:T21阳性符合率为86.8%;T18阳性符合率为76.9%;T13,阳性符合率33.3%;性染色体数目异常的阳性符合率47.1%。其它染色体异常经染色体核型分析确诊4例,经SNP array芯片检测或Fish验证后确诊8例异常核型。在4145例核型结果分析中异常核型检出率为4.46%(185/4145)。其中DS高风险异常核型检出率3.87%(60/1573);高龄孕妇的异常核型检出率为5.54%(89/1605);临界风险异常核型异常检出率2.82%(20/684);B超异常、不良孕史、生育史孕妇异常核型检出率5.65%(16/283)。在1329例核型分析和BoBs检测中,核型分析的异常核型检出率为6.70%(89/1329);BoBs检测异常检出率为7.08%(94/1327)。其中染色体数目异常73例:21-三体48例,18-三体11例,13-三体2例,性染色体数目异常(X/Y)12例,以上核型分析结果与BoBs检测均一致。另有17例BoBs检测异常结果:核型分析确诊微缺失/微重复3例;其余14例经SNP array验证确诊:4例Xp22.31~Xq27.3微缺失,6例Yp11.2~Yq11.23微缺失,2例22q11.21微重复、2例5p15微重复,2例威廉姆斯综合征(7q11.2微缺失),1例Wolf-Hirschhom综合征(4p16.3微缺失),而BoBs检测出了嵌合比例大于20%染色体核型4例,未检出染色体核型的平衡易位。结论 NIPT联合染色体核型分析和产前BoBs检测,比单一的染色体核型分析提高了11.89%(22/185)异常检出率。因此,多种平台联合的产前筛查/诊断技术提高了染色体异常检出率,降低了出生缺陷的发生率,对出生缺陷的防控起到了最有效的关键作用。更多还原

【Abstract】 Objective:To investigate the chromosomal abnormalities such as fetal Down′s syndrome(DS)and chromosomal microbes(P<0.05),and to explore the feasibility of multi-platform technique such as fetal free noninvasive gene prenatal detection(NIPT)combined with chromosome core analysis and bacterial artificial chromosome microbead analysis. Deletion/micro-repetitive syndrome detection model,evaluation of multi-platform combined with prenatal diagnosis to reduce the clinical application of birth defects. Methods:From January 2016 to April 2017,there were 4135 pregnant women who received NIPT testing and 4145 pregnant women with prenatal diagnosis indications. NIPT suggested abnormalities of cases and those with prenatal diagnosis. The patients underwent intermittent amniotic fluid puncture,amniotic fluid chromosome karyotype analysis and prenatal BoBs detection,fetal DS syndrome and other chromosomal aneuploidy and a variety of chromosome deletion/repetitive syndrome were diagnosed. Results:In 10 735 cases of NIPT detection,suggesting that the signal abnormalities in 115 cases,the detection rate was 1.07%(115/10 735). The abnormal detection rate was 1.55%(58/3742)in the elderly group and 1.48%(36/2437)in the high risk group. The abnormal detection rate was 0.46%(21/4556)in the other groups. The positive rate of T21 was 86.8%;the coincidence rate of T18 was 76.9%;T13,the coincidence rate was 33.3%;the positive rate of chromosomal abnormalities was 47.1%. Other chromosomal abnormalities were diagnosed by chromosome karyotype analysis in 4 cases,by SNP array chip detection or fish validation confirmed 8 cases of abnormal karyotype. The abnormal karyotype detection rate was 4.46%(185/4145)in the 4145 karyotype analysis. The detection rate of abnormal karyotype was 8.54%(89/1605). The abnormal detection rate of karyotype abnormality was 2.82%(20/684);B-abnormal,poor pregnancy history,fertility history of pregnant women abnormal karyotype detection rate of 5.65%(16/283). The abnormal rate of karyotype analysis was 6.70%(89/1329)in the 1329 karyotype analysis and BoBs detection. The detection rate of abnormal detection of BoBs was 7.08%(94/1327). Among them,there were 73 cases of abnormal chromosome number:48 cases of 21-trisomy,11 cases of 18-trisomy,2 cases of 13-trisomy and 12 cases of abnormal chromosome number(X/Y). The karyotype analysis was consistent with that of BoBs The There were 17 cases of BoBs detection abnormalities:karyotype analysis confirmed microdeletion/micro-repetition in 3 cases;the remaining 14 cases by SNP array validation confirmed:4 cases Xp22.31 ~ Xq27.3 microdeletion,6 cases Yp11.2~ Yq11. 23 microdeletions,2 cases of 22 q11.21 micro-repeat,2 cases of 5 p15 micro-repeat,2 cases of Williams syndrome(7 q11.2 microdeletion),1 case of Wolf-Hirschhom syndrome(4 p16.3 microdeletion),and BoBs Four cases were found that the chimeric ratio was more than 20%,and the chromosomal karyotype was not detected. Conclusion:NIPT combined with chromosome karyotype analysis and prenatal BoBs detection,compared with a single chromosome karyotype analysis increased 11.89%(22/185)abnormal detection rate. Therefore,a variety of platform combined prenatal screening/diagnostic techniques to improve the detection rate of chromosomal abnormalities,reducing the incidence of birth defects,prevention and control of birth defects played the most effective and crucial role.更多还原