目的分析颈项透明层(nuchal translucency,NT)增厚胎儿中拷贝数变异(copy number variations,CNV)的检出率和特点,以及NT增厚与CNV的关系。方法选取2017年1月至2021年12月在内蒙古自治区妇幼保健院经孕早期超声检查NT≥2.5 mm,且后续接...目的分析颈项透明层(nuchal translucency,NT)增厚胎儿中拷贝数变异(copy number variations,CNV)的检出率和特点,以及NT增厚与CNV的关系。方法选取2017年1月至2021年12月在内蒙古自治区妇幼保健院经孕早期超声检查NT≥2.5 mm,且后续接受介入性产前诊断的334例单胎孕妇及其胎儿为研究对象,收集其产检信息、遗传学检测结果及妊娠结局。遗传学检测方法包括G显带核型分析和染色体微阵列分析(chromosomal microarray analysis,CMA)。按NT厚度、NT合并其他染色体异常高危因素分别分组分析不同临床特征下NT增厚与CNV发生率的关系。结果①共发现26例CNV,检出率为7.78%。其中,13例为致病性CNV,2例为可能致病性CNV,11例为临床意义未明的(variant of uncertain significance,VOUS)CNV。15例中13例致病性及可能致病性CNV终止妊娠,11例中9例VOUS CNV病例活产并正常发育。②不同NT厚度组间CNV的检出率,以及单纯NT增厚与NT增厚合并其他高风险因素间CNV检出率均差异无统计学意义。③26例中有9例(34.6%)为复发性微缺失微重复区域的CNV,其中5例在15q11.2区域和3例在16p12.2-13.1区域。结论CNV是NT增厚胎儿常见的遗传变异,且多数为致病性和可能致病性CNV。但NT增厚程度及是否合并其他产前筛查高危因素与CNV的发生率无明显相关性。复发性微缺失微重复区域的CNV出现频率较高值得引起关注。展开更多
Fetal malformations are very frequent in industrialized countries.Although advanced maternal age may affect pregnancy outcome adversely,80%-90%of fetal malformations occur in the absence of a specific risk factor for ...Fetal malformations are very frequent in industrialized countries.Although advanced maternal age may affect pregnancy outcome adversely,80%-90%of fetal malformations occur in the absence of a specific risk factor for parents.The only effective approach for prenatal screening is currently represented by an ultrasound scan.However,ultrasound methods present two important limitations:the substantial absence of quantitative parameters and the dependence on the sonographer experience.In recent years,together with the improvement in transducer technology,quantitative and objective sonographic markers highly predictive of fetal malformations have been developed.These markers can be detected at early gestation(11-14 wk)and generally are not pathological in themselves but have an increased incidence in abnormal fetuses.Thus,prenatal ultrasonography during the second trimester of gestation provides a"genetic sonogram",including,for instance,nuchal translucency,short humeral length,echogenic bowel,echogenic intracardiac focus and choroid plexus cyst,that is used to identify morphological features of fetal Down’s syndrome with a potential sensitivity of more than 90%.Other specific and sensitive markers can be seen in the case of cardiac defects and skeletal anomalies.In the future,sonographic markers could limit even more the use of invasive and dangerous techniques of prenatal diagnosis(amniocentesis,etc.).展开更多
Introduction: A novel three dimensional approach for aneuploidy screening in the first trimester of pregnancy was developed in which risk assessment derives directly from comparing the plotted data of nuchal transluce...Introduction: A novel three dimensional approach for aneuploidy screening in the first trimester of pregnancy was developed in which risk assessment derives directly from comparing the plotted data of nuchal translucency, pregnancy associated plasma protein A (PAPP-A), and free β-human chorionic gonadotropin (fβ-hCG) of an examined fetus with similar coordinates of fetuses with already known health status. Under this approach, it is possible to utilize either a ‘box’ or a ‘sphere’ model. In either case, optimal volume sizes and the benefits of adopting a ‘minimum number of required fetuses’ (MNR) have not yet been investigated;and for the box model, two modifications, called ‘empty box results positive’ (EB+) and ‘simulation’ (SIM), provide additional options. It was the aim of this study to analyze which of the two models and their variants provides the best test performance. Methods: The study cohort was divided into a reference collective (n = 10,954) and a test collective (n = 4239). The test collective was examined repeatedly, with another model and modification used on each occasion. Test performances were compared by the area under curve (AUC) of receiver operating characteristics (ROC) curves. Results: The sphere model was inferior to the box model when optimal volumes were used with the latter and combined with the modifications EB+ and Sim. EB+ increased the number of assessable fetuses while Sim improved the test performance. MNR improved neither the box nor the sphere model. Conclusion: A new, optimized model in line with the obtained results should be developed and tested in further studies.展开更多
文摘目的 分析46,XX睾丸型性发育异常胎儿的基因型与表型,并进行文献复习。方法 1例超声提示胎儿颈后透明层增厚的孕妇来我院产前诊断中心咨询。因其符合产前诊断指征,遂行胎儿染色体核型检测、胎儿染色体基因芯片检测。以“46,XX男性综合征”、“产前诊断”、“46,XX睾丸型性发育异常”、“prenatal diagnosis”、“46,XX male syndrome”、“46,XX testicular disorder of sex development”为检索词,检索中国知网、万方数据库、PubMed数据库(建库至2023年2月底),选取产前诊断为46,XX睾丸型性发育异常胎儿且临床资料完整的文献进行复习并总结胎儿表型。结果 胎儿染色体核型正常(46,XX),基因芯片提示Yp11.31-p11.2区域拷贝数为1,大小为3299 kb,存在SRY基因,胎儿被诊断为46,XX睾丸型性发育异常。文献检索发现仅报道9例产前诊断为46,XX睾丸型发育异常(SRY基因阳性)胎儿,大部分(70%, 7/10)胎儿孕期无明显异常,其中3/10的胎儿存在结构异常或超声提示NT增厚,其中5/10孕妇存在高龄风险。结论 在产前诊断中,发现46,XX睾丸型性发育异常胎儿是极为罕见的。孕期46,XX睾丸型性发育异常胎儿无明显异常;由于CMA检测的局限性,部分46,XX睾丸型DSD胎儿(SRY基因阴性)会被漏诊,这些因素给产前诊断和遗传咨询带来极大的挑战。
基金Supported by FESR P.O.Apulia Region 2007-2013-Action 1.2.4(grant number 3Q5AX31)the National Council of Research Project AMOLAB
文摘Fetal malformations are very frequent in industrialized countries.Although advanced maternal age may affect pregnancy outcome adversely,80%-90%of fetal malformations occur in the absence of a specific risk factor for parents.The only effective approach for prenatal screening is currently represented by an ultrasound scan.However,ultrasound methods present two important limitations:the substantial absence of quantitative parameters and the dependence on the sonographer experience.In recent years,together with the improvement in transducer technology,quantitative and objective sonographic markers highly predictive of fetal malformations have been developed.These markers can be detected at early gestation(11-14 wk)and generally are not pathological in themselves but have an increased incidence in abnormal fetuses.Thus,prenatal ultrasonography during the second trimester of gestation provides a"genetic sonogram",including,for instance,nuchal translucency,short humeral length,echogenic bowel,echogenic intracardiac focus and choroid plexus cyst,that is used to identify morphological features of fetal Down’s syndrome with a potential sensitivity of more than 90%.Other specific and sensitive markers can be seen in the case of cardiac defects and skeletal anomalies.In the future,sonographic markers could limit even more the use of invasive and dangerous techniques of prenatal diagnosis(amniocentesis,etc.).
文摘Introduction: A novel three dimensional approach for aneuploidy screening in the first trimester of pregnancy was developed in which risk assessment derives directly from comparing the plotted data of nuchal translucency, pregnancy associated plasma protein A (PAPP-A), and free β-human chorionic gonadotropin (fβ-hCG) of an examined fetus with similar coordinates of fetuses with already known health status. Under this approach, it is possible to utilize either a ‘box’ or a ‘sphere’ model. In either case, optimal volume sizes and the benefits of adopting a ‘minimum number of required fetuses’ (MNR) have not yet been investigated;and for the box model, two modifications, called ‘empty box results positive’ (EB+) and ‘simulation’ (SIM), provide additional options. It was the aim of this study to analyze which of the two models and their variants provides the best test performance. Methods: The study cohort was divided into a reference collective (n = 10,954) and a test collective (n = 4239). The test collective was examined repeatedly, with another model and modification used on each occasion. Test performances were compared by the area under curve (AUC) of receiver operating characteristics (ROC) curves. Results: The sphere model was inferior to the box model when optimal volumes were used with the latter and combined with the modifications EB+ and Sim. EB+ increased the number of assessable fetuses while Sim improved the test performance. MNR improved neither the box nor the sphere model. Conclusion: A new, optimized model in line with the obtained results should be developed and tested in further studies.
