To assess the efficacy of copy number variation sequencing (CNV-seq) and karyotyping for prenatal detection of chromosomal abnormalities in fetuses with increased nuchal translucency. Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities. There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5–3.4 mm, 38.64% in the NT group of 3.5–4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05). The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5–3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis.

目的:通过分析胎儿半椎体畸形病例的临床资料,为胎儿半椎体畸形的妊娠期管理、产前诊断和遗传咨询提供临床策略.方法:对胎儿超声检查发现胎儿半椎体畸形的孕妇进行系统超声筛查和磁共振(MRI)检查,并采集胎儿组织和夫妻双方外周血进行拷贝数变异检测(CNV-seq)及家系全外显子组检测(Trio-WES).结果:胎儿系统超声筛查和胎儿MRI结果均提示胎儿半椎体、T8-S1椎体排列不整齐,CNV-seq未检出明确致病的基因组拷贝数变异(CNVs),Trio-WES检出TBX6基因c.172dup新发致病性变异,可导致常染色体显性遗传的脊柱肋骨发育不全5型(SCD5),该变异为首次报道.结论:胎儿半椎体畸形应通过胎儿系统性超声、MRI进行检查,并建议进行产前诊断明确遗传病因.相对于常规染色体核型分析和CNVs检测,WES能提高导致胎儿半椎体畸形的基因异常检出率.

This study introduced whole-exome sequencing (WES) in prenatal diagnosis of fetal bowel dilatation to improve the detection outcome when karyotype analysis and copy number variation sequencing (CNV-seq) were uninformative in detecting pathogenic variants. The work reviewed 28 cases diagnosed with fetal bowel dilatation and analyzed the results of karyotype analysis, CNV-seq, and WES. Among the 28 cases, the detection rate in cases with low risk of aneuploidy was 11.54% (3/26), which is lower than 100% (2/2) in cases with high risk of aneuploidy. Ten low-risk aneuploidy cases with isolated fetal bowel dilatation had normal genetic testing results, while the remaining 16 cases with other ultrasound abnormalities were detected for genetic variants at a rate of 18.75% (3/16). The detection rate of gene variation was 3.85% (1/26) by CNV-seq and 7.69% (2/26) by WES. This study suggested that WES could reveal more genetic risk in prenatal diagnosis of fetal bowel dilatation and has value in prenatal diagnosis to reduce birth defects.

目的 探讨基因组拷贝数变异检测（CNV-seq）联合染色体核型分析在评估胎儿心室强光点超声软指标中的临床应用价值。方法 收集2017年6月至2020年12月于华中科技大学同济医学院附属同济医院妇产科胎儿系统超声诊断为心室强光点（EIF）的143例孕妇，羊膜腔穿刺术抽取羊水，羊水标本行染色体核型分析和拷贝数变异检测。结果 143例心室强光点胎儿羊水标本中，核型分析共检出8例异常结果，异常率为5.59%;CNV-seq共检出8例致病性拷贝数变异（pCNV），异常率5.59%，联合检测共发现9例异常结果，异常率6.29%。心室强光点合并其他单个和多个超声软指标组，染色体异常率分别为8.70%和25.00%，明显高于孤立性心室强光点组（0.00%），差异有统计学意义。心室强光点合并非整倍体筛查高风险时，染色体异常率25.00%，明显高于筛查低风险组（4.58%）。结论 孤立性心室强光点不会增加胎儿染色体异常的风险，心室强光点合并其他超声软指标异常或非整倍体筛查高风险时，染色体畸变的风险显著增加。此外，在核型分析的基础上应用CNV-seq能够检测出额外的染色体异常，减少漏诊和出生缺陷的发生。

The maternal-fetal immune disorder is considered to be an important factor of preterm birth (PTB); however, the underlying mechanism is still not fully understood. This study was designed to explore the innate and adaptive immune features in the decidua during term and preterm labor. Women delivered at term or preterm were classified into four groups: term not in labor (TNL, N=19), term in labor (TL, N=17), preterm not in labor (PNL, N=10), and preterm in labor (PIL, N=10). Decidua basalis and parietalis were collected and analyzed for macrophage subtypes (M1 and M2) as well as T helper 1 (Th1), Th2, Th17 and regulatory T (Treg) cells by flow cytometry and immunohistochemistry. Our results demonstrated significantly decreased frequencies of M2 cells and elevated M1/M2 ratio in the PIL group compared to that in the PNL group in both decidua basalis and parietalis, whereas no significant differences were found between the above two groups in both sites in terms of the polarization status of Th cells. On the contrary, macrophage subsets were comparable in the TL and TNL groups, whereas elevated Th1 percentages and Th1/Th2 ratio were observed in TL women compared to that in TNL women in the decidua. Interestingly, although the frequencies and ratios of Th17 and Treg were comparable among the four groups, the Th17/Treg ratios of these groups were significantly increased in decidua basalis than that in decidua parietalis. Collectively, the M1/M2 imbalance is associated with the breakdown of maternal-fetal immune tolerance during PTB, whereas the aberrant Th1/Th2 profile plays an important role in immune disorder during term labor. Moreover, Th17/Treg deviation is more remarkable in decidua basalis than in decidua parietalis.

目的 系统评价孕期牙周病与妊娠期糖尿病(gestational diabetes mellitus,GDM)发生风险的相关性.方法 计算机检索PubMed、Web of Science、CBM、CNKI数据库,搜集有关牙周病和GDM的研究,检索时限均从建库至2021年10月23日.由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.4软件进行Meta分析.结果 共纳入11个研究,包括2 910例孕妇.Meta分析结果显示:孕期患牙周病的孕妇发生GDM的风险是正常组孕妇的1.81倍[OR=1.81,95％CI(1.31,2.50),P=0.000 3].结论 当前证据表明,孕期牙周病与GDM的发生风险存在正相关.受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证.

目的:利用全外显子测序(WES)技术分析胎儿肠管增宽的致病性突变,为产前诊断及遗传咨询提供帮助.方法:对3例肠管增宽的胎儿进行染色体核型分析、拷贝数变异(CNV)及WES检测.结果:3例胎儿染色体核型分析结果均正常,1例胎儿CNV检出15号染色体微重复,3例胎儿WES结果均发现与肠管增宽相关的基因突变.病例1为GDNF基因c.329G>A杂合变异,遗传自其父亲,可引起先天性巨结肠症3型,该病为常染色体显性遗传,并具有低外显率的特点;病例2为NOTCH2基因的c.1310A>C新发变异,与Alagille综合征2型、Hajdu-Cheney综合征相关,均为常染色体显性遗传;病例3为SLC26A3基因复合杂合突变,包括来自父亲的c.1427del突变和来自母亲的c.269_270 dup突变,可导致常染色体隐性遗传的先天性失氯性腹泻1型.经Sanger验证病例1为临床意义未明突变,根据既往病史判断该突变可能致病,病例2及病例3均为致病性突变.结论:WES技术对于分析胎儿肠管增宽的遗传变异具有重要的诊断价值.

目的 探讨正常大小卵巢癌综合征的临床特点、诊断标准及预后.方法 回顾性分析2016年1月～2019年12月在我院治疗及病理证实的35例正常大小卵巢癌综合征患者临床资料,按照组织学来源是否为第二苗勒系统将其分为苗勒组(n=30)与转移组(n=5),比较两组临床表现及预后差异.结果 苗勒组年龄、绝经人数高于转移组,差异有统计学意义(P＜0.05);两组孕次、产次比较,差异无统计学意义(P＞0.05);两组腹痛、阴道流血或流液、体检肿瘤标志物增高、胸闷气促发生率及CA125、CEA比较,差异无统计学意义(P＞0.05),苗勒组腹胀发生率、腹水含量高于转移组,CA199低于转移组,差异有统计学意义(P＜0.05);苗勒组患者行全子宫切除+双附件切除+大网膜切除+盆腔淋巴结清扫术,转移组患者行全子宫切除+双附件切除+大网膜切除+盆腔淋巴结清扫术;苗勒组主要为卵巢原发肿瘤和卵巢外腹膜浆液性乳头状腺癌,转移组主要为来源于胃、阑尾、直肠、消化道的肿瘤;苗勒组9例误诊,转移组2例误诊;两组存活时间比较,差异无统计学意义(P＞0.05).结论 对于正常大小卵巢癌综合征患者,必须高度重视鉴别诊断,尽早手术探查,尽量切除癌灶,术后辅以有效化疗或放疗,以期获得最佳生存期和预后.

目的:探讨胎儿肠管增宽的临床表现与妊娠结局之间的相关性,为临床咨询、判断预后和指导治疗提供依据.方法:回顾分析2015年10月至2019年6月于华中科技大学附属同济医院胎儿系统超声诊断为肠管增宽的51例孕妇的临床资料.结果:51例孕妇中,19例妊娠结局良好,32例出现不良妊娠结局(引产、胎死宫内、新生儿死亡、出生后需手术治疗等),占62.7％.胎儿十二指肠增宽的不良结局发生率为100％,明显高于小肠增宽(54.2％)及结直肠增宽(25.0％).孕32周前诊断胎儿肠管增宽不良妊娠结局发生率为72.7％,而孕32周后检出者为44.4％.胎儿肠管增宽合并羊水过多22例,不良结局发生率为86.4％,明显高于羊水量正常孕妇(40.0％).10例孕妇行羊膜腔穿刺产前诊断均未发现异常,2例十二指肠增宽新生儿行基因检查为21-三体综合征.结论:产前超声诊断胎儿肠管增宽与消化系统畸形及妊娠结局密切相关,及时发现、密切随访、早期处理极为重要.

Liddle 综合征(Liddle Syndrome)又称假性醛固酮增多症,是一种罕见的单基因致病型高血压,遗传方式为常染色体显性遗传,遗传学基础是编码ENaC 的基因(SCNN1B 和SCNN1G)发生功能获得性突变,主要特征包括高血压、低钾血症、低肾素及低醛固酮血症等,常于青少年起病.该病常有家族聚集性,也存在散发情况,由 Grant Liddle 等于 1963年首次进行详细描述.现将我们收集的一个家系的临床特点、基因检测结果及产前诊断报告如下.