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我国是人口出生缺陷高发国家,总发生率5%~6%,每年新增约90万例出生缺陷儿,给家庭和社会带来沉重的负担[1-2]。在政府部门的重视及干预下,一些防控措施行之有效,如叶酸增补、将产前筛查和产前诊断纳入民生工程、免费新生儿疾病筛查等。同时,广大科研及医务工作者也在不断探索更加灵敏和精准的出生缺陷检测方法。胎儿无创DNA产前检测,具有检测率高、灵敏度高、特异性强的特点,在孕妇及妇产科医生中备受青睐。本文对于我中心实验室进行无创DNA检测的5 077名孕妇中结果为阳性的64名孕妇,进行羊水穿刺核型分析验证无创DNA检测结果,并对妊娠结局进行随访,探讨无创DNA产前基因检测在产前筛查诊断中的作用。
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接受无创DNA检测的5 077例孕妇中结果为阳性高风险者64例,包括21-三体28例,18-三体4例,13-三体3例,性染色体异常14例,其他染色体异常8例,微缺失微重复7例。其中54例接受羊水穿刺,诊断率为84.4%,其中21-三体24例,确诊23例,1例为21-三体微重复,经父母验证,微重复来源于母亲;18-三体4例,确诊2例;13-三体3例,确诊1例;性染色体异常11例,确诊5例;其他染色体异常6例,确诊0例;微缺失微重复6例,确诊2例。1例无创DNA结果阴性,因超声检查提示多发异常,羊水穿刺结果证实为18-三体(见表 1)。对无创DNA检测结果阳性而未做羊水穿刺核型分析者进行电话随访跟踪,结果见表 2。
类型 无创DNA检测阳性例数 羊水穿刺数据 例数 确诊例数 核型分析 符合率/% 21-三体 28 24 23 23例确诊21-三体, 1例21染色体微重复,来自孕妇本人 95.8 18-三体 4 4 2 2例确诊18-三体, 2例正常 50.0 13-三体 3 3 1 1例确诊13-三体, 2例正常 33.3 性染色体异常 14 11 5 3例47,XO;1例47,XXY, 1例XYY 45.5 其他染色体异常 8 6 0 正常 0.0 微缺失微重复 7 6 2 1例三体7号微重复,1例双胎之一为21-三体微重复,1例为双胎之一15q11.2-13.14.79Mb重复 33.3 合计 64 54 33 61.1 表 1 无创DNA检测阳性结果及羊水穿刺核型分析结果
类型 无创DNA检测阳性例数 妊娠结局 21-三体 4 2例胎死宫内,2例引产 性染色体异常 3 1例失访; 1例45, XO/46, XX; 1例无异常 其他染色体异常 2 2例外观均无异常 微缺失微重复 2 1例胎死宫内,1例无异常 表 2 未做羊水穿刺结局分析
无创DNA检测结果为高风险孕妇的产前诊断结果及妊娠结局分析
Analysis of the prenatal diagnosis and pregnancy outcome in 64 high risk cases with positive results of non-invasive DNA testing
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摘要:
目的探讨无创DNA检测结果为阳性的高风险孕妇产前诊断结果及妊娠结局。 方法对无创产前DNA检测的5 077名孕妇外周血中游离胎儿DNA进行二代测序,检查结果为阳性者建议进一步做羊水穿刺进行细胞核型分析确认,并进行电话追踪随访。 结果5 077名受检孕妇中检测结果为高风险者64例,包括21-三体28例,18-三体4例,13-三体3例,性染色体异常14例,其他染色体异常8例,微缺失微重复7例。54例进行了羊水穿刺,其中21-三体24例,确诊23例;18-三体4例,确诊2例;13-三体3例,确诊1例;性染色体异常11例,确诊5例;其他染色体异常6例,确诊0例;微缺失微重复6例,确诊2例。1例无创DNA检测结果为阴性,因超声检查提示多发异常,羊水穿刺结果证实为18-三体。 结论无创DNA产前检测对21-三体综合征的阳性预测值较高,但仍有假阳性和假阴性的发生,不能完全代替核型分析;无创DNA产前检测对18-三体综合征和13-三体综合征阳性预测值仍存在很大偏差,但其可检测到微缺失微重复异常,具有染色体核型分析不可代替的优越性。 Abstract:ObjectiveTo analyze the antenatal diagnosis and pregnancy outcome in high risk pregnant women with positive results of the non-invasive prenatal DNA testing, and discuss its clinical significance. MethodsThe non-invasive prenatal DNA testing in 5 077 pregnant women were implemented, the free fetal DNA in maternal peripheral blood of the second generation was sequenced.The positive was confirmed by the cell karyotype detected by amniocentesis, and followed up by telephone. ResultsAmong 5 077 pregnant women detected by non-invasive prenatal DNA testing, the high risk in 64 cases was identified, which included 28 cases of 21-trisomy, 4 cases of 18-trisomy, 3 cases of 13-trisomy, 14 cases of sexual chromosome abnormality, 8 cases of other chromosome abnormality and 7 cases of microdeletion and microduplication.Amniocentesis was performed in 54 cases, the results showed that 23 cases were confirmed among 24 cases of 21-trisomy, 2 cases were confirmed among 4 cases of 18-trisomy, 1 case was confirmed among 3 cases of trisomy, 5 cases were confirmed among 11 cases of sex chromosome, no case was confirmed among 6 cases of other chromosomes, and 2 cases were confirmed among 6 cases of micro deletion and micro duplication.The non-invasive DNA testing results showed 1 case was negative, the ultrasound examination suggested the multiple abnormalities, and the amniocentesis result showed which was the 18-trisomy. ConclusionsThe positive predictive value of 21-trisomy syndrome is higher by the non-invasive prenatal DNA testing, but the false positive and false negative result still occur, which cannot completely replace karyotype analysis.The non-invasive DNA prenatal testing is still far from the positive predictive value of 18-trisomy syndrome and 13-trisomy syndrome, but it can detect micro-deletion and micro-repetition abnormalities, which has irreplaceable superiority over the karyotype analysis. -
Key words:
- prenatal testing /
- amniocentesis /
- karyotype analysis
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表 1 无创DNA检测阳性结果及羊水穿刺核型分析结果
类型 无创DNA检测阳性例数 羊水穿刺数据 例数 确诊例数 核型分析 符合率/% 21-三体 28 24 23 23例确诊21-三体, 1例21染色体微重复,来自孕妇本人 95.8 18-三体 4 4 2 2例确诊18-三体, 2例正常 50.0 13-三体 3 3 1 1例确诊13-三体, 2例正常 33.3 性染色体异常 14 11 5 3例47,XO;1例47,XXY, 1例XYY 45.5 其他染色体异常 8 6 0 正常 0.0 微缺失微重复 7 6 2 1例三体7号微重复,1例双胎之一为21-三体微重复,1例为双胎之一15q11.2-13.14.79Mb重复 33.3 合计 64 54 33 61.1 表 2 未做羊水穿刺结局分析
类型 无创DNA检测阳性例数 妊娠结局 21-三体 4 2例胎死宫内,2例引产 性染色体异常 3 1例失访; 1例45, XO/46, XX; 1例无异常 其他染色体异常 2 2例外观均无异常 微缺失微重复 2 1例胎死宫内,1例无异常 -
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