Reiss Rosemary E, Discenza Marie, Foster Judith, Dobson Lori, Wilkins-Haug Louise
Center for Fetal Medicine and Prenatal Genetics, Brigham and Women's Hospital, Boston, MA, USA.
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA.
Prenat Diagn. 2017 May;37(5):515-520. doi: 10.1002/pd.5039.
To assess the incidence of sex chromosome aneuploidy (SCA) predicted by noninvasive prenatal testing (NIPT), assess test performance, and compare it with nuchal translucency (NT) screening among patients seen in our prenatal diagnosis center.
We identified suspected cases of SCA by reviewing results from all NIPT samples sent from our center to commercial laboratories offering analysis by cell-free DNA between 1 December 2012 and 31 July 2015. Records of pregnancies positive for SCA were reviewed for ultrasound findings, NIPT indications, and karyotype results on maternal, fetal, and postnatal samples. Other SCA cases presenting during this period regardless of NIPT status were identified from genetic counseling and cytogenetics laboratory logbooks.
Noninvasive prenatal testing predicted SCA in 18/2851 patients (0.63%). All had diagnostic testing of fetal or newborn samples. No patients terminated pregnancies on the basis of NIPT. NIPT suggested triple X in five cases, two with elevated NT: all were confirmed on karyotype. Two Klinefelter syndrome cases were also accurately predicted by NIPT. NIPT indicated monosomy X in 11 cases. Only one was a true positive. Ten were false positives, with 46, XX found on fetal or newborn karyotype. Maternal karyotype was mosaic (45, X[4], 46, XX[26]) in one case. Over the same time period, four additional cases of 45, X were confirmed on fetal samples, all with cystic hygromas. One of these had had a false negative NIPT result. The remaining patients pursued only direct testing via CVS or amniocentesis.
Sex chromosome aneuploidy was frequently suspected on NIPT. False positive rate for monosomy X was surprisingly high (91%). Prediction of other SCA was more accurate. Diagnostic fetal chromosome analysis should be offered after abnormal NIPT or in the presence of cystic hygromas despite normal NIPT. NIPT limitations should be explained in pretest counseling. © 2017 John Wiley & Sons, Ltd.
评估通过无创产前检测（NIPT）预测的性染色体非整倍体（SCA）的发生率，评估检测性能，并将其与我们产前诊断中心患者的颈部透明带（NT）筛查结果进行比较。
通过回顾2012年12月1日至2015年7月31日期间从我们中心送往提供游离DNA分析的商业实验室的所有NIPT样本的结果，确定SCA疑似病例。对SCA检测呈阳性的妊娠记录进行回顾，以查看超声检查结果、NIPT指征以及母体、胎儿和产后样本的核型结果。从遗传咨询和细胞遗传学实验室日志中识别出在此期间出现的其他SCA病例，无论其NIPT状态如何。
无创产前检测在2851例患者中预测出18例SCA（0.63%）。所有患者均对胎儿或新生儿样本进行了诊断性检测。没有患者基于NIPT终止妊娠。NIPT提示5例为XXX，其中2例NT升高：所有病例经核型分析均得到证实。NIPT还准确预测出2例克兰费尔特综合征病例。NIPT提示11例为X单体。仅1例为真阳性。10例为假阳性，胎儿或新生儿核型显示为46,XX。1例患者的母体核型为嵌合体（45,X[4],46,XX[26]）。在同一时期，另外4例胎儿样本经证实为45,X，均伴有颈部水囊瘤。其中1例NIPT结果为假阴性。其余患者仅通过绒毛取样（CVS）或羊膜穿刺术进行直接检测。
无创产前检测经常怀疑存在性染色体非整倍体。X单体的假阳性率出奇地高（91%）。对其他SCA的预测更准确。NIPT结果异常或尽管NIPT结果正常但存在颈部水囊瘤时，应提供胎儿染色体诊断分析。应在检测前咨询中解释NIPT的局限性。©2017约翰威立国际出版公司。
