Uterine corpus endometrial carcinoma (UCEC), a prevalent malignancy in the female reproductive system, has witnessed a 30% increase in recent year. Recognizing the significance of early treatment in reducing patient mortality, the identification of potential biomarkers for UCEC plays a crucial role in early diagnosis. This study was to identify key genes associated with UCEC utilizing the Gene Expression Omnibus database, followed by validating their prognostic value across multiple databases. Analysis of four UCEC databases (GSE17025, GSE36389, GSE63678, GSE115810) yielded 72 co-expressed genes. KEGG and GO enrichment analyses revealed their involvement in physiological processes such as transcriptional misregulation in cancer. Constructing a protein-protein interaction network for these 72 genes, the top 10 genes with significant interactions were identified. Survival regression analysis highlighted NR3C1 as the gene with a substantial impact on UCEC prognostic outcomes. Differential expression analysis indicated lower expression of NR3C1 in UCEC compared to normal endometrial tissue. Cox regression analysis, performed on clinical datasets of UCEC patients, identified clinical stage III, clinical stage IV, age, and NR3C1 as independent prognostic factors influencing UCEC outcomes. The LinkedOmics online database revealed the top 50 positively and negatively correlated genes with NR3C1 in UCEC. Subsequent investigations into the relationship between NR3C1 and tumor-infiltrating immune cells were conducted using R software. Gene set enrichment analysis provided insights into NR3C1-related genes, showing enrichment in processes such as Ribosome, Oxidative phosphorylation in UCEC. Collectively, these comprehensive analyses suggest that NR3C1 may serve as a potential biomarker indicating the prognosis of UCEC.

Omphalocele is a midline abdominal wall defect of variable size, which occurs at the root of the umbilical cord. The surface is a sac membrane composed of amnion, Wharton′s jelly and peritoneum, and the sac contains herniated abdominal contents. This birth defect is the most common fetal abdominal wall defect, and the incidence rate in China is about 3.38/10 000. Omphalocele, which contains the hepatic tissue, can be diagnosed antenatally by transvaginal ultrasound as early as 9-10 weeks of gestation. Omphalocele has a high correlation with chromosome aneuploid. In addition to chromosomal abnormalities, it is also associated with genetic syndromes according to literature reports. This article introduces the pregnant management and transport after delivery of a case of fetal omphalocele treated by us, and reviews the relevant literature.

Rationale: Uterine artery spontaneous rupture is a rare but potentially life-threatening complication during pregnancy and puerperium. The lack of typical symptoms makes it difficult to diagnose, which can result in serious consequences for both the mother and fetus. Patient concerns: Case 1 presented with fainting and lower abdominal discomfort, while Case 2 developed hypotension after delivery and remained in poor condition even after rehydration. Diagnoses: Both cases were diagnosed with uterine artery spontaneous rupture, with intraoperative findings revealing ruptures in different branches of the uterine artery. Interventions: Both cases underwent surgical interventions, with laparoscopic surgery performed in Case 1 and repair of the ruptured artery in Case 2. Outcomes: Both cases had successful outcomes, with the ruptured arteries repaired and the patients discharged from the hospital within a week after surgery. Lessons: Uterine artery spontaneous rupture is a rare but potentially life-threatening complication that may present with atypical symptoms. Early diagnosis and prompt surgical intervention are crucial in preventing serious complications for both the mother and fetus. Clinicians should maintain a high level of suspicion for this condition when evaluating patients presenting with unexplained symptoms or signs of peritoneal irritation during pregnancy and puerperium.

目的 探讨CTCF基因致病突变的产前遗传学分析及咨询.方法 运用染色体核型分析、荧光原位杂交技术(FISH)、染色体微阵列分析(CMA)及全外显子组测序技术(WES)对一例产前超声发现双侧肾脏回声增强结构模糊的胎儿进行产前遗传学检测.结果 核型分析、荧光原位杂交技术、染色体微阵列分析未见异常,家系全外显子测序检测到胎儿CTCF基因存在新发变异c.944_951dup,为移码突变,导致318位甘氨酸密码子(GGT)被替换为组氨酸密码子(CAC),并在第18个密码子后终止(p.Gly318Hisfs*18),产生截短蛋白质.CTCF基因突变可致罕见常染色体显性智力障碍21型,胎儿期尚未见报道.结论 本例为首次在胎儿期检出CTCF基因致病突变,推测双肾回声增强结构模糊为该基因突变相关的一种新的胎儿期表型.全外显子组测序技术在产前检测出罕见致病突变的病例需重视检测前后的咨询.

Pfeiffer综合征(Pfeiffer syndrome,PS)的产前诊断十分困难,通过超声影像结合基因分析可协助诊断,FGFR2 基因c.870G>C(p.W290C)突变是本病例的致病原因,产前诊断发现上述位点突变导致PS在我国尚属首次,现报告如下.

This article reports a pedigree with two previously deceased neonates. Both neonates did not experience asphyxia but passed away on their 5th and 13th day of life. The chromosomal analysis of the parents' karyotype revealed no abnormalities. Clinical manifestations of the two deceased cases and relevant medical records were recollected. Whole exome sequencing was conducted on the stem blood sample of Neonate 2, revealing a c.729_730insTT homozygous mutation (p.D244Lfs*39) in the methylmalonyl-CoA mutase gene (NM_000255). It was confirmed that Neonate 2 was affected with methylmalonic acidemia. Amniocentesis was performed at 20 +3 weeks in the current pregnancy. Sanger sequencing of amniotic fluid indicated that the fetus carried the same gene mutation as Neonate 2. Consequently, the fetus was expected to be a patient with methylmalonic acidemia and to exhibit the same phenotype as Neonate 2. Termination of pregnancy, therefore, was selected at 24 weeks of gestation.

Trisomy 11 mosaicism is clinically rare, for which making diagnostic and treatment decisions can be challenging. In this study, we used noninvasive prenatal testing, chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing and fluorescence in situ hybridization for detecting trisomy 11 mosaicism in two cases and provided them with genetic counseling. In one of the cases, the fetus with confined placental mosaicism trisomy 11 presented with severe growth restriction and a placental mosaic level of 44%, and pregnancy was terminated at 25+3 weeks of gestation. In the other case with true low-level fetal mosaicism of trisomy 11, the pregnancy continued after exclusion of the possibility of uniparental disomy and structural abnormalities and careful prenatal counseling. The newborn was followed up for more than one year, and no abnormality was found. Noninvasive prenatal testing is capable of detecting chromosomal mosaicism but may cause missed diagnosis of true fetal mosaicism. For cases with positive noninvasive prenatal testing but a normal karyotype of the fetus, care should be taken in prenatal counseling and pregnancy management.

Abstract Objectives To investigate the efficiency of the upgraded noninvasive prenatal test (NIPT-Plus) in fetuses with increased nuchal translucency (NT). Methods Fetuses with an increased NT at or above 2.5 mm were selected for prenatal diagnosis. Amniotic fluid was collected from all cases for karyotype analysis and copy number variation sequencing (CNV-seq), and cell-free fetal DNA (cfDNA) in maternal blood was tested using Noninvasive Prenatal Test (NIPT-Plus) before amniocentesis in some cases. The results of amniocentesis with different NT thicknesses were analyzed and compared with those of NIPT-Plus. Results A total of 125 eligible patients were divided into group A (2.5 mm ≤ NT < 3.0 mm) and group B (NT ≥ 3.0 mm). In group A, the detection rate of chromosomal aneuploidy and pathogenic copy number variation (CNV) was 10.6% and 6.4%, respectively. The total chromosome abnormality rate in group B (34.7%) was significantly higher than that in group A (17%). In 72 patients who underwent NIPT-Plus and amniocentesis, chromosomal aneuploidy accounted for 80.8% of the total chromosomal abnormalities. Among 21 cases of chromosomal aneuploidy, NIPT-Plus detected 20 cases. The sensitivity and specificity of NIPT-Plus toward aneuploidy detection were 95.2% and 100%, respectively. Among the five cases of pathogenic CNV, only two were detected using NIPT-Plus. Conclusion NIPT-plus is recommended as the first choice for fetal diagnosis in pregnant women with 2.5 mm ≤ NT < 3.0 mm who do not accept invasive prenatal diagnosis. When NT ≥ 3.0 mm and NIPT-Plus detects chromosomal aneuploidy, a rapid prenatal diagnosis can be performed through amniocentesis. In cases where NIPT-Plus yields negative results, amniocentesis still needs to be performed to detect chromosome microdeletions/duplications in order to avoid a missed diagnosis.

RAS/丝裂原激活蛋白激酶(RAS/mitogen-activited protein kinase,RAS/MAPK)信号通路参与调控细胞增殖、分化、存活、凋亡、免疫应答等行为,编码RAS/MAPK信号通路蛋白的基因发生突变,可引起RAS信号通路相关综合征(RASopathies)[1],其发病率约为1/1000.RAS基因包含NRAS (neuroblastoma-RAS)、HRAS(harvery-RAS)、KRAS (kirsten-RAS)等,编码由上游调节子激活的小三磷酸鸟苷(guanosine triphosphate,GTP)酶单体,激活多种信号通路,传递胞外信号启动下游信号通路,包括RAS/MAPK通路[2].RAS/MAPK信号通路失调会引起淋巴发育不良、先天性心脏病、肺动脉瓣狭窄、男性隐睾、青春期发育迟缓等,外观上的典型表现为低耳位、高睑缘、上睑下垂、宽颈、胸廓脊柱畸形等.另外RAS/MAPK信号通路在介导胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)的细胞内信号转导中也起着重要作用,IGF-1介导生长激素的出生后生长效应 [3],身材矮小是各型RASopathies患者的共同特征.

Objective:To analyze the indications for invasive prenatal diagnosis in the third trimester and summarize the pregnant outcome.Methods:Clinical data of 121 women who underwent invasive prenatal diagnosis in the third trimester in the prenatal diagnostic center of the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020 was retrospectively analyzed. Different genetic diagnostic methods were used according to different indications. Indications and results of prenatal diagnosis, as well as the complications within two weeks after the invasive procedure, pregnancy outcome, and neonatal follow-up of all the participants were described.Results:Among the 121 cases, 107 cases underwent amniocentesis, seven underwent percutaneous umbilical blood sampling, and seven had both procedures performed at the same time (one underwent thoracocentesis at the same time). Newly identified ultrasound abnormalities in the second and third trimesters were the main indications for prenatal diagnosis, accounting for 99.2%(120/121), of which short limbs and fetal growth restriction accounted for 25.0% (30/120) and 20.0% (24/120), respectively. Genetic abnormalities and congenital diseases were detected in 20 cases with a detection rate of 16.5%(20/121). Among them, there were nine cases of achondroplasia, five cases of pathogenic copy number variations, one case of achondroplasia with pathogenic copy number variation, one trisomy 18, one 47,XXX, one tetrasome mosaicism of 12p, one de novo WTX c. 1072(Exon2) C>Tp.R358X heterozygous mutation, and one fetal hypoproteinemia. In addition, six cases with copy number variation of unknown significance (VUS) were detected, noting for a detection rate of 5.0%(6/121). Among the 20 cases with abnormal detection, 15 were terminated, two delivered prematurely before obtaining the prenatal diagnosis results, one underwent cesarean section before obtaining prenatal diagnostic results and two continued the pregnancies. In the six cases with VUS, one was terminated and the other five continued the pregnancy. Only one case had preterm premature rupture of membranes 2 d after amniocentesis and the incidence rate of complications after all kinds of invasive procedures was 0.8% (1/121). During the neonatal follow-up, postnatal whole exome sequencing revealed monogenetic disorder in two cases with normal prenatal diagnostic results; the patient with 12p chimerism had developmental delay; the one with WTX mutation deceased on the day of born; the rest newborns developed normally. Conclusions:As a relatively safe method, invasive prenatal diagnosis in the third trimester is of great importance and value in reducing the miss diagnostic rate of fetuses with severe genetic diseases and birth defects. The appropriate application of prenatal whole exome sequencing could further help to decrease the miss diagnostic rate of monogenetic disorder.

Cardiovascular and respiratory effects of intracerebroventricular (icv) administration of neuropeptide Y (NPY) and separate, preferential agonists for NPY Y1 and Y2 receptors were observed in anaesthetised dogs. Central injections of NPY resulted in significant cardiac slowing and decreases in arterial pressure. These cardiovascular effects were blocked by central injection of the NPY Y1-preferring antagonist 1229U91. Central injection of NPY did not have a significant effect on ventilation, but the NPY Y1 antagonist 1229U91 administered alone caused a significant increase in ventilation. The NPY Y1-receptor agonist [Leu31Pro34] NPY significantly decreased ventilation while the NPY Y2 receptor agonist N-acetyl [Leu28Leu31] NPY 24–36 significantly increased it. A similar inverse relationship was seen with respect to blood pressure, with the NPY Y1-receptor agonist [Leu31Pro34] NPY significantly decreasing blood pressure, while the NPY Y2 receptor agonist N-acetyl [Leu28Leu31] NPY 24-36 significantly increased it. These findings suggest a role for NPY Y1 receptors in pathways mediating decreases in ventilation and blood pressure, and for NPY Y2 receptors in those mediating increased ventilation and blood pressure.

Objective:To explore the relationship between the prenatal ultrasound characteristics of fetal bilateral hyperechogenic kidneys and pregnancy outcomes, in order to provide a reference for prenatal consultation of such disease.Methods:From January 2015 to December 2018, 26 cases of fetal bilateral hyperechogenic kidneys were diagnosed by prenatal ultrasound at the First Medical Center of PLA General Hospital, which were divided into either an induced labor/death group (19 cases) or a survival group (7 cases). Fisher exact probability test was used to compare the differences in ultrasonic characteristics between the two groups, including corticomedullary differentiation (CMD), medulla echogenicity, amniotic fluid volume, kidney volume, cyst, and extrarenal malformation.Results:There were 10 cases with CMD, of which 7 survived and 3 underwent induced labor, 16 cases with CMD absence/reversal, of which none survived, 9 cases with normal medullary echo, of which 6 survived and 3 underwent induced labor, and 17 cases with abnormal medullary echo, of which none survived. There were statistically significant differences between the survival group and the induced labor /death group in CMD and medulla echogenicity (P＜0.001 and =0.002, respectively), but there were no statistically significant differences in amniotic fluid volume, kidney volume, cyst, or extrarenal malformation (P＞0.05 for all). CMD and medulla echogenicity were significantly correlated with pregnancy outcome (r=0.768 and 0.652, respectively; P＜0.01 for both), while amniotic fluid volume, kidney volume, cyst, and extrarenal malformation were not significantly correlated with pregnancy outcome (P＞0.05 for all).Conclusion:When fetal bilateral kidneys are hyperechogenic, CMD absence/reversal and medullary echogenicity are significantly associated with adverse pregnancy outcomes, and significantly increase the risk of fetal mortality and long-term kidney impairment.

目的:探讨胎儿软骨发育不全（ACH）的疾病特点。方法:回顾性分析2010年1月至2020年6月于解放军总医院第一医学中心行一代测序检测发现成纤维细胞生长因子受体3（FGFR3）基因c.1138位点突变的胎儿共15例的临床资料（包括超声测量指标）。对胎儿父母的年龄，胎儿的头围（HC）、股骨长（FL）、腹围（AC）、双顶径（BPD）、羊水量、超声检查异常等结果进行描述性统计分析，计算各指标的比值或Z值［即测量值与相应孕周标准值之差的标准差（SD）倍数］。ΔZ H-F表示股骨发育相对于头部发育落后的SD倍数；ΔZ H+A-2F表示股骨发育相对于头部和腹部发育落后的SD倍数。 结果:15例患儿中，妊娠中期出现表型者3例（3/15），妊娠晚期发现表型者12例（12/15）。检测孕周范围为23周 +5~33周 +4。15例胎儿母亲的年龄为（29.8±3.6）岁（范围：24~38岁），其中2例（2/15）为高龄（年龄 ≥35岁）；胎儿父亲的年龄为（31.1±4.8）岁（范围：22~41岁），其中3例（3/15）高龄（年龄 ≥35岁）。15例（15/15）胎儿均出现股骨短小（Z FL<-2.00），Z FL值为-4.73±1.08。3例（3/15）胎儿出现头大（Z HC>2.00）。FL/HC和FL/AC分别为0.151±0.014和0.172±0.012，均小于正常值。ΔZ H-F和ΔZ H+A-2F分别为5.65±1.95与10.04±2.75，提示胎儿基因异常的风险性高。1例孕妇出现羊水过多表型（1/15），羊水指数为31.4 cm。2例胎儿出现中枢神经系统异常（2/15），其中1例为右侧脑室轻度扩张，1例为胎儿丘脑后上方中线部位囊性结构。 结论:胎儿ACH存在明显的妊娠中晚期股骨短小的特点，BPD增大及其他伴随症状不明显。建议对于妊娠中晚期发现股骨明显短小的胎儿行FGFR3基因c.1138位点检测以明确ACH的诊断。

目的 在住院医师规范化培训中推广"翻转课堂"理念,总结妇产科专业基地的实践经验,提高培训效果.方法 选取解放军总医院第一医学中心妇产科专业基地2016、2017级住院医师共20人,均观察2年,2016级学员观察时间为2016年9月至2018年8月,2017级学员观察时间为2017年9月至2019年8月.每位住院医师按照抽签顺序依次进行"学员to学员"授课.上述培训模式的住院医师属于教学改革组,另有2018级的14名住院医师(观察时间为2018年9月至2020年8月)作为传统教学组进行对照.由带教老师分别为住院医师评分,以评价学员各方面能力的提升程度,并通过问卷调查形式收集并归纳住院医师对该教学形式的反馈意见.结果 教学改革组培训后自学、专业知识掌握程度、临床思维、语言表达方面的评分高于培训前(P<0.05),但培训前后学员的科研能力比较,差异无统计学意义(P>0.05);两组学员在规范化培训开始前综合能力比较,差异无统计学意义(P>0.05),通过规范化培训,两组学员的综合能力均明显高于培训前(P<0.05),且教学改革组高于传统教学组,差异有统计学意义(P<0.05);相对于传统教学组,教学改革组的学员对"学员to学员"这一授课形式的教学认同感较高,65％学员认为语言表达能力和查阅专业相关资料的能力得到明显提高.结论 在妇产科规范化培训教学中应用"翻转课堂"教学模式满足了住院医师个性化学习和自主学习的需求,促进了学习动机与态度的转变,为妇产科专业基地的教学改革带来新的途径.

Objective To investigate the genetic etiology of skeletal dysplasia in highly selected fetuses during the first and second trimesters using deep phenotyping and exome sequencing (ES). Method Fetuses with short femurs were identified using the established prenatal diagnostic approach. A multidisciplinary team reviewed fetal phenotypic information (prenatal ultrasound findings, fetal postmortem, and radiographs) in a cohort of highly selected fetuses with skeletal dysplasia during the first and second trimesters. The affected families underwent multiplatform genetic tests. Results Of the 27 affected fetuses, 21 (77.8%) had pathogenic or potential pathogenic variations in the following genes: COL1A1, FGFR3, COL2A1, COL1A2, FLNB, DYNC2LI1, and TRIP11. Two fetuses had compound heterozygous mutations in DYNC2LI1 and TRIP11, respectively, and the other 19 carried de novo autosomal dominant variants. Novel variants were identified in COL1A1, COL2A1, COL1A2, DYNC2LI1, and TRIP11 in 11 fetuses. We also included the first description of the phenotype of odontochondrodysplasia in a prenatal setting. Conclusions ES or panel sequencing offers a high diagnostic yield for fetal skeletal dysplasia during the first and second trimesters. Comprehensive and complete phenotypic information is indispensable for genetic analysis and the expansion of genotype-phenotype correlations in fetal skeletal abnormalities.

背景 拉森综合征(Larsen syndrome OMIM 150250)是一种由FLNB基因突变导致的常染色体显性遗传综合征,其特点为双侧肘关节脱位、髋部脱位、膝关节脱位、外翻足以及铲状指.目的 明确1例宫内超声提示关节挛缩胎儿其家系的遗传学病因,为遗传咨询和再生育指导提供依据.方法 2015年5月于解放军总医院第一医学中心妇产科招募到1例出现宫内关节畸形的孕妇,与孕妇及家属详细交待病情,考虑到胎儿存在严重致残或致死性畸形,孕妇及家属要求引产.遂于孕25+2周行引产术.取引产儿大腿内侧肌肉组织及父母外周血进行基因检测.结果 该家系的基本临床病史信息未见异常,引产儿娩出后出现明显双侧肘关节和膝关节挛缩固定、双拇指呈铲状指、双手指末端关节固定挛缩、双侧踝关节扭曲固定、脚背部过伸、马蹄足畸形等拉森综合征样表型.目标外显子(panel)测序结果为FLNB基因c.565(E3)T>C(p.189,W>R)杂合突变,经一代测序验证双亲及第二胎基因型为野生型,无明显临床表型.结论 我们通过目标外显子(panel)家系测序明确了拉森综合征的致病位点为c.565(E3)T>C(p.189,W>R),为此家系的遗传咨询与再孕指导提供了有益信息.

目的 探讨产褥感染的病原菌分布情况及妊娠结局.方法 回顾性分析2010年1月至2020年12月在解放军总医院第一医学中心收治的产褥感染病例,统计微生物学特征、分娩方式、产程情况、妊娠结局等.结果 2010年1月至2020年12月本院收治的孕产妇共22 159例,产褥感染55例,外院转诊19例;患者平均最高体温为(39.36±0.76)℃,细菌感染导致血流感染率为41.8％(23/55),脓毒血症发生率为7.3％(4/55),脓毒性休克发生率为20.0％(11/55),切除子宫发生率为9.1％(5/55),死亡率为1.8％(1/55).大肠埃希菌感染导致发生血流感染率为42.8％(12/28),脓毒血症发生率为7.1％(2/28),脓毒性休克发生率为14.3％(4/28),切除子宫发生率为7.1％(2/28).活产33例中出现新生儿窒息9例,其中早期新生儿死亡1例,窒息患儿中7例因大肠埃希菌感染导致.结论 感染仍是导致孕产妇死亡及严重并发症的重要原因之一,临床应给予高度重视.大肠埃希菌是导致孕产妇感染的主要菌种,可导致母儿严重不良结局.

AbstractBackgroundSkeletal disorders, which have great genotypic and phenotypic varieties, are a considerable challenge to differentiate these diseases and provide a definitive prenatal diagnosis or pre‐implantation. The present study aims to identify the causative mutation in two unrelated outbred Han–Chinese families.MethodTwo short‐limb fetuses were referred to our hospital. Genomic DNA was extracted from the amniotic fluid of the short‐limb fetuses and from peripheral blood of their parents. To identify the causative gene, next‐generation‐based target capture sequencing was performed on these two fetuses, followed by Sanger Sequencing in unrelated healthy controls. Segregation analysis of the candidate variant was performed in parents by using Sanger sequencing. The mutations were analyzed by SIFT, PolyPhen and Provean.ResultsWe found that fetal genetic skeletal dysplasia was confirmed according to the correlations between genetic mutations and phenotypes in two Chinese families. Targeted next generation sequencing was performed to screen causative mutations in patients. Two novel heterozygous mutations COL1A1 c.1706 G > C (p. G569A) and c.3307 G > A (p. G1103S) were respectively identified. The results suggested that COL1A1 novel mutations were in highly conserved glycine residues present in the Gly‐X‐Y sequence repeats of the triple helical region of the collagen type I α chain, which was responsible for Osteogenesis Imperfecta. The presence of the missense mutation was also confirmed with the Sanger sequence. These two mutations were predicted to be pathogenic by SIFT, PolyPhen and Provean.ConclusionOur findings showed that the mutations of COL1A1 may play important roles in fetal genetic skeletal dysplasia in Chinese patients. Exome sequencing enhances the accurate diagnosis in utero then provides appropriate genetic counseling.

目的 评估无创产前筛查(non-invasive prenatal test,NIPT)技术在临床应用中的价值.方法 回顾性分析2016年1月-2018年6月在解放军总医院进行NIPT筛查的病例数据共计8410例,入组数据为有随访或产前诊断结局者7707例,分别按年龄、筛查适应证等分组.比对NIPT在不同组别的阳性预测值、阴性预测值、敏感度、特异性、假阳性率、假阴性率等指标.结果 1)年龄≥35岁(高龄)组2978例,总高风险28例,高风险率为0.94％(28/2978),产前诊断确诊阳性21例,阳性预测值为75％,阴性预测值100％,敏感度100％,特异性99.76％,假阳性率0.237％,假阴性率0.<35岁年龄组4729例,总高风险48例,高风险率为1.02％(48/4729),产前诊断确诊阳性28例,阳性预测值60.87％,阴性预测值99.96％,敏感度93.33％,特异性99.62％,假阳性率0.383％,假阴性率6.67％.两组阳性预测值、阴性预测值、敏感度、特异性差异无统计学意义(P>0.05).2)传统血清学筛查高风险591例和临界风险值1480例样本经NIPT二次筛查后高风险为15例,需进行产前诊断的例数从591例减少到15例,产前诊断结果证实为10例真阳性,5例为假阳性.结论 NIPT用于胎儿染色体非整倍体检测是目前筛查技术中的最佳选择,可用于高龄人群一线筛查,也可用于传统血清血筛查后的二次筛查.

Meckel–Gruber syndrome (MKS) is a clinically and genetically heterogeneous ciliopathy characterized by a triad of occipital encephalocele, polycystic kidneys, and postaxial polydactyly. Pathogenesis of MKS is related to dysfunction of primary cilia. However, reports on MKS caused by Tectonic2 (TCTN2) mutations are scanty whilst. There is no direct evidence of ciliogenesis in such MKS patients. Here, we identified two novel nonsense variants of TCTN2 (c.343G > T, p.E115*; c.1540C > T, p.Q514*) in a Chinese MKS fetus. Compared to reported TCTN2-causing MKS patients, our case represented an endocardial pad defect, which was not reported previously. We also found primary cilia protruded normally from the surface of epithelial cells in the affected fetal kidney tubules compared to controls, indicating TCTN2 is not necessary for ciliogenesis in the kidney. To our knowledge, this is the first case of MKS fetus caused by TCTN2 mutations from China.