NIPT对临床意义不明基因组拷贝数变异的效能评估一项基于28911例队列的多中心大样本研究  

Evaluation of the efficacy of NIPT in detecting copy number variations in non-syndromic genomes: A multicenter large sample study based on the 28 911 cohort

作　　者：杨丽[1] 韩锐[1] 腊晓琳[1,2,3,4] Yang Li;Han Rui;La Xiaolin(Center for Reproductive Medicine,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China;Research Center for Integrated Prevention and Treatment of Reproductive Diseases and Birth Defects,Xinjiang Medical University,Urumqi 830017,China;Xinjiang Clinical Research Centre for Reproductive Immunology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China;State Key Laboratory of Pathogenesis,Prevention,and Treatment of High Incidence Diseases in Central Asia,Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学第一附属医院生殖医学中心,乌鲁木齐830011 [2]生殖疾病与出生缺陷综合防治研究中心,乌鲁木齐830017 [3]新疆生殖免疫临床医学研究中心,乌鲁木齐830011 [4]新疆医科大学省部共建中亚高发病成因与防治国家重点实验室,乌鲁木齐830011

出　　处：《国际遗传学杂志》2024年第2期93-105,共13页International Journal of Genetics

基　　金：新疆医科大学第一附属医院青年科研启航专项基金(2022YFY-QKQN-65);新疆维吾尔自治区自然科学基金(2022D01C467);国家自然科学基金(81960289)。

摘　　要：目的探讨无创产前DNA检测(non-invasive prenatal test,NIPT)在胎儿临床意义不明基因组拷贝数变异(copy number variations,CNVs)中的效能评估,以期分析NIPT在此类染色体异常筛查中的有效性和可行性。方法回顾性分析2018年1月13日至2023年8月30日期间多中心的28911例单胎孕妇的NIPT筛查结果。NIPT提示临床意义不明CNVs异常信号者,知情同意后行有创产前诊断进一步做染色体G显带核型分析和基于下一代测序的基因组拷贝数分析(copy number variation sequencing,CNV-seq)检测。并根据CNVs片段大小和胎儿超声结果进一步划分亚组,以评估NIPT在不同条件下检测临床意义不明CNVs的性能。结果NIPT共筛查到175例临床意义不明CNVs,其中108例(66.5%)进一步行产前诊断。经CNV-seq确认后,NIPT筛查临床意义不明CNVs的阳性预测值(positive predictive value,PPV)为25.9%。检测到的CNVs片段大小相差1 Mb范围内的占62.9%。从亚组来看,NIPT筛查效能在颈项透明层(nuchal translucency,NT)增厚组最高(PPV为60.0%),胎儿超声异常者的PPV高于超声正常组P=0.017。NIPT在<5 Mb(PPV为30.00%)和≥10 Mb(PPV为37.5%)的预测能力较强,对≥5 Mb且<10 Mb预测能力较弱。在CNVs<5 M且胎儿超声结果正常的情况下,有13例出现CNVs异常,除4例自行终止妊娠外,其余胎儿均无异常。结论NIPT对临床意义不明CNVs预测能力较低,并且这类孕妇大多数妊娠结局良好,特别是对于超声正常的胎儿,扩大NIPT的检测范围,可能增加产前诊断率和引起非必要的妊娠终止,遗传咨询及生育管理至关重要。Objective To explore the efficacy evaluation of non-invasive prenatal testing(NIPT)in fetal variants of unknown significance genomic copy number variations(CNVs),aim to analyze the effectiveness and feasibility of NIPT in screening for such chromosomal abnormalities.Method A retrospective analysis was conducted on the NIPT screening results of 28911 singleton pregnant women from multiple centers between January 13,2018 and August 30,2023.NIPT suggests that individuals with abnormal signals of variants of unknown significance CNV should undergo invasive prenatal diagnosis with informed consent for further chromosome G-banding karyotype analysis and genome copy number variation sequencing(CNV-seq)based on next-generation sequencing.And further divided into subgroups based on the size of CNV fragments and fetal ultrasound results to evaluate the performance of NIPT in detecting variants of unknown significance CNVs under different conditions.Result A total of 175 variants of unknown significance CNV cases were screened by NIPT,of which 108 cases(66.5%)underwent further prenatal diagnosis.After confirmation by CNV-seq,the positive predictive value(PPV)of variants of unknown significance CNVs screened by NIPT was 25.9%.62.9%of the detected CNVs had a difference in fragment size within the range of 1 Mb.From a subgroup perspective,the NIPT screening efficacy is highest in the nuchal translucency(NT)thickening group(PPV of 60.0%),and the PPV of fetal ultrasound abnormalities is higher than that of ultrasound normal groups P=0.017.NIPT has strong predictive ability for<5 Mb(PPV30.00%)and≥10 Mb(PPV37.5%),but weak predictive ability for≥5 Mb and<10 Mb.In the case of CNVs<5 Mb and normal fetal ultrasound results,there were 13 cases with abnormal CNVs.Except for 4 cases of spontaneous termination of pregnancy,all other fetuses showed no abnormalities.Conclusion NIPT has a low predictive ability for variants of unknown significance CNV,and most of thest pregnant women have good pregnancy outcomes,especially for fetuses wi

关 键 词：出生缺陷 无创产前DNA检测 临床意义不明基因组拷贝数变异 产前筛查 效能评估 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]