Background Chromosomal abnormalities are one of the common causes of birth defects,and karyotype analysis is still an important method for prenatal diagnosis of chromosomal abnormalities as well as an effective way to prevent and control birth defects.However,karyotype analysis,especially chromosomal image segmentation and classification mainly depends on manual work at present,which is laborious and time-consuming.As an emerging approach to karyotype analysis,it is of great significance to investigate the application value of artificial intelligence(AI)in prenatal chromosomal karyotype diagnosis.Objective To investigate the application effect and clinical value of AI in prenatal karyotype diagnosis.Methods A total of 1 000 pregnant women who received interventional prenatal diagnosis and karyotype analysis of amniotic fluid cells in the department of medical genetics and prenatal diagnosis of Wuxi Maternity and Child Health Care Hospital between 2020 and 2022 were selected as the study subjects.The karyotype analysis of all cases was performed using two-line mode,the results of the AI reading were reviewed by one geneticist in the first line,and another geneticist analyzed the karyotypes by Ikaros karyotype analysis workstation in the second line,the diagnostic results and time were recorded respectively.The final diagnosis of the samples were based on the manual review of the first line and the manual reading of the second line.Results Among the 1 000 amniotic fluid samples,735 cases were diagnosed as normal karyotype,233 cases as aneuploidy,0 case as structural abnormality and 32 cases as mosaicism by AI.The numbers of normal karyotype,aneuploidy,structural abnormality and mosaicism assessed by AI-assisted geneticist were 689,233,45 and 33,which were completely consistent with those evaluated by geneticist using Ikaros system.Compared with AI-assisted geneticist,AI-based diagnosis had strong consistency(Kappa=0.895,95%CI=0.866-0.924,P<0.01).The diagnostic accuracy,sensitivity and positive predictive value of AI-based diagnosis was 95.4%,95.4%and 100.0%,respectively,among which the normal karyotype,aneuploidy,structural abnormality and mosaicism were detected with a sensitivity of 100.0%,100.0%,0 and 97.0%,and the positive predictive value of 100.0%,100.0%,0 and 100.0%.The average diagnostic time of AI was shorter than that of AI-assisted geneticist and Ikaros-assisted geneticist(P<0.001),and AI-assisted geneticist took less time on average to diagnose than the Ikaros-assisted geneticist(P<0.001).Conclusion AI-assisted karyotype analysis of amniotic fluid cells has a high degree of automation,but its ability to recognize chromosomal structural abnormalities needs to be improved.It is suggested that AI be combined with the geneticist for karyotype analysis in clinical application to ensure the quality of prenatal diagnosis and improve efficiency.

Objective:To investigate the ultrasonographic and genetic features of Cri-du-chat syndrome (CDCS).Methods:In this retrospective study, cases with CDCS diagnosed in Wuxi Maternal and Child Health Care Hospital from 2004 to 2021 and with complete data were reviewed to describe and analyze the maternal serum prenatal screening, non-invasive prenatal testing (NIPT), ultrasound, genetic examination data, and pregnancy outcomes.Results:All cases were diagnosed by karyotype analysis, seven of them were diagnosed prenatally through amniotic fluid, and four were diagnosed after birth through peripheral blood. Five of the seven cases diagnosed prenatally had an abnormal serological screening, including two cases with 5p- indicated by NIPT. Of the 11 cases, prenatal ultrasonography showed cerebellar transverse diameter less than －2 SD in eight cases, including four with cerebellar hypoplasia (CH), two with fetal growth restriction, and two with cranial diameters less than －2 SD. One case was shown with an increased nuchal translucency, accompanying bilateral choroid plexus cysts of the lateral ventricles, and suspected persistent left superior vena cava. No obvious ultrasound abnormality was observed in the remaining two cases. Among the seven cases diagnosed prenatally, excluding one case that refused parental verification, further single nucleotide polymorphism array (SNP array) showed that all six cases inherited the de novo mutations from the parents. The cytogenetic analysis found the breakpoints at 5p13, 5p14, and 5p15 in five, three, and three cases. All seven pregnancies were terminated in the second trimester. Four children diagnosed postnatally presented with CDCS phenotype during the follow-up at three years old. Conclusions:Fetal CDCS should be considered with CH detected by prenatal ultrasonography, though the correlation between CH and CDCS still needs further investigation. Gene mapping with an SNP array is helpful for phenotypic profiling and genetic counseling.

目的 确定FMR1基因CGG重复序列正常型、中间型和前突变型在无锡地区育龄妇女中的分布情况.方法 应用PCR技术对我院产前诊断中心育龄妇女(18～49岁)120例外周血样本进行FMR1基因的CGG重复序列进行检测.用GeneMapper 4.0软件分析毛细管电泳结果,用SPSS 11.0软件进行数据分析.结果 120例受检者中无前突变及全突变检出.共检测到2例灰区携带者,其余118例(CGG)n重复数范围为21 ～44,其中(CGG)n重复数为28和29的占所有受检者的最高.结论 本文为首次在无锡地区普通育龄期妇女开展的FMR1基因突变携带频率的研究,为今后筛查试验的可行性提供数据.

Objective To establish the median equation of serum free β-human chorionic gonadotropin (free β-HCG), pregnancy-associated plasma protein A (PAPP-A) in the first trimester in Wuxi, and to evaluate the influence of the local adjustment of the median equation on the screening efficiency. Methods A total of 5,294 gravidas [9 to 13 (+6) gestational weeks] underwent a screening test of double serum markers including free β-HCG, PAPP-A by automatic time-resolved fluorescence immunoassay analyzer (TRFIA). The risks of Downs syndrome, Edward syndrome were evaluated by Life Cycle 4.0 software. The median values of free β-hCG, PAPP-A were analyzed with statistical software, and the median regression equation of free β-hCG and PAPP-A in suited local pregnant women with different gestational weeks was established. Then the risks of the screening data were re-evaluated. Combined with prenatal diagnosis of chromosomal karyotype results and pregnancy outcomes and pregnant women followed up, the screening efficiency between the two median equa-tions was compared. Results Compared with gaucasian markers of built-in software, the median level for serum β-HCG and PAPP-A were higher on average respectively after revised gestational age and weight (freeβ-HCG: P>0.05, PPAPP-A: P<0.05). The detection rates for trisomy 21 were 85.4% in local median equation and 71.4% in the software built-in one. The faulse positive rates for trisomy 21 were 4.59% in local median equation and 4.74%% in the software built-in one. Conclusions There are significant differences on the race and region when using the LifeCycle 4.0 median equations. It is very important to establish the local median equation based on revised gestation age and weight in the first trimester for prenatal serum screening test. Adjusted local median can help to improve the screening efficiency of prenatal screening.

目的 联合应用染色体核型分析及芯片检测,对一例反复缺陷儿妊娠史有再生育需求夫妇进行产前诊断与遗传咨询,为有效预防出生缺陷提供诊疗思路.方法 夫妇双方及本次妊娠胎儿进行G显带染色体核型分析,采用微阵列比较基因组杂交(array-based comparative genomic hybridization,array-CG H)技术排除致病性染色体微缺失微重复.结果 丈夫核型为46,XY,t(5;6)(p13;p25),孕妇核型正常,胎儿染色体核型46,XN,结合第二胎猫叫综合征(Cri-du-Chat syndrome,CDCS)引产史,考虑为父源性CDCS;array-CGH检测未发现致病性拷贝数变异(Copy number variation,CNV);孕妇继续妊娠并顺产健康男婴,随访至今无异常.结论 细胞与分子遗传学方法相结合合理应用,可为反复缺陷儿妊娠史夫妇查找病因,减少再发风险,改善妊娠结局,达到优生优育的目的.

目的 分析181例羊水染色体异常的临床资料,探讨其遗传咨询与处理方式以合理指导妊娠结局.方法:2008年1月-2013年12月,无锡市妇幼保健院产前诊断中心对4 879例具有产前诊断指征孕妇行羊膜腔穿刺、羊水细胞培养、G显带核型分析.获得染色体报告后,予以遗传咨询,跟踪随访胎儿妊娠结局.结果 4 879例羊水细胞中,共检出异常核型181例,阳性检出率3.71％.异常核型中,各项高危指征所占比例分别为产前筛查高风险40.33％、高龄16.02％、夫妻一方染色体异常13.26％、超声软指标异常8.29％、无创高风险6.63％、不良孕产史4.42％、具有两项以上指征11.05％.异常核型的遗传咨询:①染色体数目异常尤其是常染色体数目异常的胎儿,建议终止妊娠;②嵌合体复查脐血验证,并结合临床、超声资料慎重给予建议;③来源不明的mar染色体,运用不同显带方式,必要时加做父母染色体,采用分子遗传方法探明来源后指导妊娠结局;④平衡易位、倒位携带者一般无异常表型但不排除少数特例,结合影像学检查情况,告知风险;⑤几例衍生染色体、环状染色体含有染色体的部分缺失、重复可产生异常表型,建议终止妊娠;⑥多态性变异一般影响不大,但应告知有生殖异常等风险.结论 ①产前诊断高危指征的孕妇,胎儿染色体异常率增加,应建议其行侵入性产前诊断;②羊水染色体核型异常的胎儿,根据不同情况,咨询医生的综合判断与个体化遗传咨询相结合、合理指导妊娠结局十分重要.

目的:将FISH技术与传统的细胞遗传性检测有机结合起来,提高产前诊断的准确率和成功率.方法:对8例有高危因素的患者进行FISH技术结合绒毛染色体培养分析的产前诊断.结果:1例绒毛染色体分析未见分裂相,1例绒毛染色体偶见5号染色体断裂,另外6例绒毛染色体分析与FISH技术检测结果完全一致.结论:绒毛染色体细胞遗传学检测结合FISH技术形成互补,是一种值得推广的产前诊断方法.

目的:探讨1种相对便捷、准确、经济的适用于杂合型SNP位点的无创性产前检测胎儿唐氏综合征的方法.方法:选择50例孕整倍体胎儿(孕15～21周)、13例孕21 三体胎儿(孕19～26周)的母血浆样本,应用Multiple-SNaPshot法检测胎盘源性PLAC4基因上5个SNP等位基因的基因比率及其杂合性,从而对杂合型SNP位点的胎儿无创性产前检测唐氏综合征;同时对我国苏南地区200例人群的5个SNP位点进行基因型别研究.结果:从63例单胎孕妇外周血中成功提取到PLAC4 mRNA,检测出17例PLAC4上为杂合型SNP的样本,通过分析SNP等位基因比率检测出14例正常整倍体胎儿及3例21三体胎儿.苏南地区人群PLAC4上Rs8130833和Rs4818219位点的杂合度分别为0.278和0.343.结论:对PLAC4基因上为杂合型SNP位点的胎儿,用Multiple-SNaPshot法检测其等位基因比率可用于无创性产前筛查唐氏综合征.苏南地区人群PLAC4基因上SNP杂合度较高的位点有Rs8130833和Rs4818219.

目的分析引起习惯性流产的病因,探讨习惯性流产的发生率,降低不良妊娠的发生。方法对185例门诊习惯性流产患者的病因进行回顾性分析。结果本组185例患者中,遗传因素染色体异常占45.95%(85/185);免疫因素占15.14%(28/185);内分泌异常占14.59%(27/185);女性生殖道感染率占12.43%(23/185);子宫病变占6.49%(12/185);不明原因占5.41%(10/185)。结论根据习惯性流产的病因分析,染色体异常占主要因素是造成胚胎丢失的重要原因,及时进行产前诊断,是防止先天缺陷以及染色体异常携带者出生的关键。

唐氏筛查是预防缺陷儿出生的重要手段之一,目前唐氏筛查高风险的结果绝大多数为阴性,同时也有一定数量的假阴性,因此,如何降低唐氏筛查假阳性率,以提高羊水产前诊断的效率,更好地为临床服务。本文就影响唐氏筛查准确性的相关问题作一简要综述。

Objective:To explore the prediction value of Down's syndrome screening in the second trimester of pregnancy in the detection of fetal chromosomal abnormality. Methods:Serum alpha-fetoprotein (AFP)、unconjugated estriol (u-E3) and β-HCG level in 15230 pregnant women(15～20+6 gestational weeks)from Jan 2008 to Oct 2009 in our hospital were detected by time-distinguished fluorescence immunoassay. Amniocentesis for fetal karyotype was done between 20 to 24 gestational weeks in gravidas with high risk by screening.The effect of Down's syndrome screening was evaluated. Results:984 cases were detected at high risk,and the positive rate was 6.46%. In which,736 cases were positive in Down's syndrome,78 cases were positive in 18-trisome,and 169 cases were positive in neural tube defects. Amniocentesis was done in 773 cases at high risk,in which 29 cases with fetal abnormal chromosome,the detectable rate was 3.75%. Among them,11 cases were Down's syndrome,1 cases was 18-trisome and 1 cases was 69,XXX. The sensitivity and specificity of Down's syndrome screening was 92.86% and 95.25%,respectively. Conclusions:Down's syndrome screening in the second trimester of pregnancy is an effective method to predict abnormal fetus and bad pregnancy outcome. Amniocentesis for fetal karyotype is useful in prenatal diagnosis.

目的:探讨解整合素-金属蛋白酶12(ADAM12)在孕早期妇女中不同孕周的正常参考值范围,为孕早期产前筛查胎儿唐氏综合征提供实验室依据.方法:收集2008年6月～2009年6月在无锡市妇幼保健院自愿参加孕早期产前筛查的孕妇静脉血血清样本共85份,-70℃保存,孕周为5～10周,常规三联产前筛查采用Wallac产筛软件,ADAM12水平检测采用时间分辨荧光免疫法,用SPSS11.5统计软件、Microsoft Excel软件对结果进行分析.结果:孕早期妇女ADAM12检测结果因孕周而异,本研究孕5周共10例,ADAM12平均值为5.68 ng/ml;孕6周共19例,ADAM12平均值为7.29 ng/ml;孕7周共26例,ADAM12平均值为70.64ng/ml;孕8周共16例,ADAM12平均值为89.40ng/ml;孕9周共10例,ADAM12平均值为111.91 ng/ml;孕10周共9例,ADAM12平均值为139.76 ng/ml.ADAM12水平随孕周增加而升高,并因孕周不同呈相关性,P＜0.05,但孕早期ADAM12水平整体偏低.结论:ADAM12在孕早期是一种有效的筛查指标,可为提前诊断唐氏综合征提供实验室依据,但目前因标本量不够大,尚不具备条件建立孕早期ADAM12的正常参考值范围.

FISH技术的基本原理是用已知的标记单链核酸为探针,按照碱基互补的原则,与待检材料中未知的单链核酸进行异性结合,形成可被检测的杂交双链核酸.

目前,唐氏筛查在国内外得到大量应用,在中国羊水产前诊断的阳性率在0%-1%之间,这就说明唐氏筛查高风险的结果绝大多数为阴性,同时也有一定数量的假阴性,因此,如何降低唐氏筛查假高风险率以提高羊水产前诊断效率就显得格外重要.

目的比较绒毛细胞染色体直接制片法和培养法的优缺点,提高产前诊断和流产绒毛细胞染色体核型分析效率。方法分别进行绒毛组织细胞培养和直接制片,通过G显带分析核型。结果培养法的成功率要远高于直接制片法,但步骤较复杂。结论在流产或早期产前诊断中,培养法的成功率和准确率要比直接法高,是一种实用的早期产前诊断和流产绒毛细胞染色体核型分析方法。

Objective The purpose of this study is to discussion the medical value of ADAM12 in second trimester prenatal screening for fetal Down's Syndrome.Methods Pregnant women voluntary to do prenatal screening during 2004-2008 years were enrolled.For 16-20 weeks gestational age,fetuses were comfirmed to be with DS by karyotype in 18 subjects.Control group were 36 subjects from the same period confirmed by a normal newborn delivery,Wallac screen software to do routine triple production prenatal screening.Detecting the serum level of ADAM12 by using time-resolved fluorescence immunoassay,spss11.5 statistical software and Microsoft Excel were used to deal with the results.Results In 18 casesof children with DS,the conventional screening detection rate was 67%,when screening by ADAM12 alone,seven cases were detected with a detection rate of 39%.When ADAM12 joint with conventional triple screening for DS,the detection of 15 cases,with a detection rate of 84%.The serum level of ADAM12 of pregnant women in two groups increases with increasing gestational age,P0.05.Between two groups,the serum level of ADAM12 trend with increasing gestational age becomes more apparent in patient group.Conclusion ADAM12 in second-trimester screening is an effective indicator,especially combined with triple screening,they will greatly enhance the detection of DS and improve diagnostic accuracy,but indicators of second-trimester screening is not yet qualified.

猫叫综合征(CDC,MIM 123450)又叫5p-综合征,是最典型的染色体缺失综合征,为第5号染色体短臂缺失,缺失区域的大小不等。由于患儿哭喊声似猫叫,因而得名。新生儿发病率为1/50000[1]本症特点为婴儿哭声柔弱如猫叫,并有生长迟缓及智能发育不全。其发病机制是破坏了基因的平衡,可能是等位基因的缺失,致隐性基因的表达相关。该病须经染色体检查确诊。我院在进行羊水染色体检查时发现一对夫妇连续孕育两胎猫叫综合征的患者。

目的 对206例早期自然流产绒毛标本染色体进行核型分析,探寻流产的原因.方法 对流产绒毛组织细胞进行直接制片法,G显带制作染色体分析.结果 206例早期流产患者绒毛标本染色体异常共41例,占19.90%,其中三倍体4例(1.94%),三体19例(9.22%),嵌合体3例(1.46%).结论 染色体异常是造成流产的重要原因之一.

目的:探讨妊娠高血压综合征(妊高征)患者血浆肾上腺髓质素(AM)、降钙素基因相关肽(CGRP)、细胞间黏附分子-1( sICAM-1)及总同型半胱氨酸(THcy)水平的变化与患者发病及其进展的关系.方法:35名非孕妇女、34名正常孕妇(对照组)及35例妊高征患者的血浆AM和CGRP含量采用放射免疫分析;血浆sICAM-1水平采用酶联免疫分析.THcy则应用化学发光免疫分析法测定.结果:表1可见,血浆AM水平对照组较非孕妇女组水平略升高,但无显著统计学意义(P＞0.05);治疗前组与对照组比较升高非常显著(P＜0.01);治疗后水平下降明显,但与对照组比较升高仍存在显著性(P＜0.05).CGRP水平对照组略低于非孕妇女组,但并不存在统计差异(P＞0.05),治疗前组与对照组比较下降非常显著(P＜0.01);经治疗水平显著升高,与对照组比较已无显著差异(P＞0.05).sICAM-1水平对照组较非孕妇女组水平略高,但无显著统计学意义(P＞0.05);治疗前组与对照组比较升高显著(P＜0.05);治疗后水平下降明显,但与对照组比较差异已无显著性(P＞0.05).THcy水平的统计学变化与sICAM-1一致.结论:妊高征患者血浆四项指标的测定对于了解和认识其发病机理及预估病情有帮助.

目的:评价经腹旋转法脐静脉穿刺术在产前诊断胎儿染色体异常中的应用。方法:对56例孕妇在超声引导下行经腹旋转法脐静脉穿刺抽取脐血检查胎儿染色体核型,并观察手术的成功率和并发症。结果:56例脐静脉穿刺中,第一次抽不出脐静脉血、通过顺时钟旋转180°,再抽取脐静脉血成功的有20例;出现胎儿心动过缓2例,脐带出血9例。结论:经腹旋转法脐静脉穿刺术是一项安全、可靠的产前诊断技术。