False-negative prenatal diagnosis of restrictive dermopathy.

Restrictive dermopathy is a rare autosomal recessive lethal skin dysplasia. It has been assumed that the characteristic morphologic abnormalities should allow a reliable prenatal diagnosis on fetal skin biopsies at about 20 weeks pregnancy. We report on a false-negative prenatal diagnosis.     

False-negative prenatal diagnosis of restrictive dermopathy

Restrictive dermopathy is a rare autosomal recessive lethal skin dysplasia. It has been assumed that the characteristic morphologic abnormalities should allow a reliable prenatal diagnosis on fetal skin biopsies at about 20 weeks pregnancy. We report on a false-negative prenatal diagnosis. © 1992 Wiley-Liss, Inc.     

Prenatal diagnosis of bullous ichthyosiform erythroderma: detection of tonofilament clumps in fetal epidermal and amniotic fluid cells.

The prenatal diagnosis of bullous ichthyosiform erythroderma (BIE) has been achieved at 20 weeks' gestation by electron microscopic identification of a pathognomonic cytoskeletal abnormality within fetal epidermal cells obtained by fetoscopic skin biopsy. The same abnormality was also observed in skin derived amniotic fluid cells. The question whether amniocentesis might be used instead of fetoscopy for future prenatal detection of BIE is discussed.     

Prenatal diagnosis of X-linked hypohidrotic ectodermal dysplasia by linkage analysis

Prenatal diagnosis of X-linked hypohidrotic ectodermal dysplasia was previously performed by the direct histological analysis of fetal skin obtained by late second trimester fetoscopy. The recent gene mapping of the locus for the disorder to the region of Xq11-21.1 now permits the indirect prenatal diagnosis of the disorder by the method of linkage analysis, based on closely linked marker loci, during the first trimester of pregnancy. We report the prenatal diagnosis of a male fetus with a high probability of the disorder by a linkage analysis utilizing restriction fragment length polymorphisms at the DXS159, PGK1, and DXS72 loci, from a DNA sample obtained by a chorionic villus biopsy at 9 weeks gestation. After further counseling, the pregnancy was terminated but the diagnosis could not be confirmed by histological analysis, even though analysis of skin samples by light and electron microscopy showed lack of hair germs, primary dermal ridges, and sweat gland primordia, due to the early developmental stage of the fetus. The use of DNA-based linkage analysis now offers the opportunity for an earlier diagnosis of X-linked hypohidrotic ectodermal dysplasia by a method other than fetal skin sampling. However, families must also fully understand the present limitations of the method prior to undertaking the procedure.     

Maternal age and recommendation of amniocentesis

We report on the prenatal diagnosis of epidermolysis bullosa letalis with pyloric atresia in a pregnancy not known to be at risk for this condition. Elevated maternal serum alphafetoprotien levels led to ultrasonography which demonstrated gastric dilatation, consistent with pyloric atresia, and echogenic particles in the amniotic fluid, the “snowflake sign,” previously described in two pregnancies of fetuses with disorders of skin sloughing. Amniotic fluid alpha-fetoprotien was markedly elevated and the acetylcholinesterase was positive. The diagnosis of epidermolysis bullosa letalis with pyloric atresia was confirmed after delivery by electron microscopy of fetal skin which showed typical changes of hypoplastic absent hemidesmosomes and separation along the dermal-epidermal junction. None of these abnormal prenatal findings are consistently present in pregnancies with epidermolysis bullosa with pyloric atresia. Thus, although useful when abnormal, when the test results are normal, the need for confirmatory fetoscopy and fetal skin biopsy remains. © 1993 Wiley-Liss, Inc.     

母血浆及血清中胎儿游离DNA的研究进展

1997年胎儿游离DNA的发现为无创性产前诊断开辟了新的途径。母血循环中的胎儿游离DNA含量相对较高,获取方法比较简单,在早孕阶段就可以检测到,这些优点成为极具潜力的无创伤性产前诊断方法。目前,胎儿游离DNA已经应用于某些性连锁疾病、妊娠相关疾病、染色体病、胎儿RhD血型检测等很多疾病的产前诊断中。我们希望此技术的进一步发展和完善可以使这种无创性的产前诊断方法在临床得到更广泛的应用。     

Prenatal diagnosis of Fanconi anemia

Prenatal diagnosis was performed on a fetus at risk for Fanconi anemia. A high spontaneous (0.30 breaks/cell) and diepoxybutane-induced (0.69 breaks/cell) chromosome breakage rate indicated an affected fetus and the pregnancy was terminated. The anatomic findings in the aborted fetus together with cytogenetic findings in cultured fetal skin fibroblasts confirmed the prenatal diagnosis.     

孕妇外周血中胎儿核酸的研究新进展

从孕妇外周血中直接提取胎儿成分进行产前诊断日益受到重视。明确胎儿细胞或者核酸在母血中的存在形式、正常含量以及病理情况下的改变,对非侵入性的产前诊断具有很重要的临床意义,同时孕妇外周血胎儿核酸在病理性产科及优生优育等方面都有了新的广泛的研究。     

孕妇血浆中胎儿DNA的检测

从孕妇外周血中分离胎儿细胞一直是遗传病非损伤性产前诊断的主要思路与探索途径。尽管在孕妇外周血中服地细胞的富集,鉴定,和遗传病的非损伤性产前诊断等方面取得了一些重要的进展,但是利用孕妇外周血中的胎儿细胞进行遗传病非损伤性产前诊断的主要障碍依然是胎儿细胞的富集效率不高,而过高的的母体背景影响检测胎儿特异等位基因。最近发现在孕妇的血浆中存在胎儿DNA,这一发现为非损伤性产前基因诊断开辟了新途径。我们结合煮沸法与硅法,建立了一种有效的,简便的,经济的从血浆中提取DNA的方法,通过调整PCR系统组成,增加循环次数,成功地从母体血浆中扩增出胎儿特异的SRY基因,同时采取严格的防污染措施,避免了假阳性或假阴性结果。我们的结果表明,应用我们建立的血浆DNA提取方法与调整的PCR系统,在孕早期可以准确地确定胎儿的性别,这对于性连锁疾病的非损伤性产前诊断具有重要意义。我们的工作为我国非损伤性产前诊断研究的开展与深入打下基础。     

Rh阴性孕妇外周血基因鉴定胎儿RhD血型的方法

目的建立可靠有效的检测孕妇外周血中胎儿游离DNA的方法,探讨其在非创伤性产前诊断中的价值。结论采用PCR技术对5例RhD阴性孕妇外周血血浆DNA进行分析,然后对出生后婴儿脐带血进行Rh血清学表型分析,回顾性评价无创性预测胎儿RhD基因分析的准确性。结果 5例RhD阴性血浆标本扩增出180bp与156bp两条特异性片段,产后新生儿脐血血清学检测结果为RhD阳性,与PCR检测结果完全吻合。结论孕妇外周血浆中胎儿游离DNA的测定能实现对胎儿RhD基因型的预测判定。孕妇外周血检测胎儿DNA可应用于非创伤性产前诊断。     

孕妇血中胎儿微小RNA等核酸在唐氏综合征无创产前诊断中的应用

唐氏综合征是最常见的染色体非整倍体遗传病,出生干预是预防该病的有效措施.传统的产前诊断具有创伤等缺陷,无创产前诊断是未来发展的需求.孕妇血胎儿细胞、胎儿游离DNA、胎儿游离RNA及胎儿游离microRNA的分析是新近发展的4种唐氏综合征无创产前诊断技术.母血胎儿游离miRNA有足够的稳定性、特异性和准确性,是最具临床应...     

产前胎儿系统超声检查对孕中晚期胎儿畸形筛查的价值

目的讨论产前胎儿系统超声检查对胎儿形态、结构畸形筛查的诊断和价值。方法对7826例（18w-40w）中晚期胎儿进行彩超产前胎儿结构和形态的系统筛查,并且按照英国胎儿基金会超声检查规范,采集21幅标准图片并进行图片存储,对产后诊断结果进行回顾性分析。结果产前超声系统筛查出192例畸形胎儿,经引产或出生后证实,漏诊8例,诊断检出率95．83％,单发畸形162例（162／192,84．37％）,多发畸形27例（27／192,14．06％）,双胎畸形3例（3／192,1．56％）。结论胎儿系统超声检查对胎儿形态、结构畸形的诊断具有重要的价值,它是产前诊断胎儿畸形的首选方法。     

长沙地区3079例产前诊断病例的染色体结果分析

目的通过分析我院3079例因各种指征行产前诊断孕妇胎儿染色体的结果,探索研究血清学产前筛查、B超产前筛查并结合产前诊断技术对降低出生缺陷的临床意义。方法对我院2004年5月至2012年12月接受产前诊断的3079位孕妇的胎儿染色体结果进行回顾性分析。结果 3079例孕妇中,发现异常染色体核型128例（128/3079）,占4.16%（不包括正常变异的倒位和异染色质增加等多态性变异23例）。其中常染色体数目异常60例（46.88%）;结构异常43例（33.59%）。性染色体异常25例（19.53%）。结论血清学产前筛查、B超产前筛查结合产前诊断技术可以有效的降低出生缺陷。     

10例胎儿腹水宫内诊断与治疗

目的对先天发育异常腹水胎儿进行脐静脉穿刺和腹水穿刺等产前诊断及宫内干预，了解胎儿腹水的病因病理，探讨胎儿腹水可行的诊疗方案。方法对10例孕23～35w，B超诊断腹水胎儿进行产前诊断，内容包括：母血Rh、ABO血型、地中海贫血、TORCH及脐静脉穿刺查胎血：血红蛋白电泳、血常规、细胞形态、染色体、TORCH及胎血生化肝功、心酶、B2－MG等指标；胎儿腹水穿刺行常规、生化、细菌学等检查；在产前诊断排除胎儿染色体、TORCH、重型地中海贫血等重大疾病基础上对胎儿进行腹水穿刺、经母补氧、补液等改善胎盘功能等对症处理。结果10例腹水胎儿5例获得良好预后；1例胎儿经干预病程向好，但其家属要求放弃；3例胎儿腹水治疗效果不满意，其中2例同意终止妊娠，另1例坚持妊娠，于34w胎死。结论胎儿不明原因腹水应该进行产前诊断，适当对症处理、观察，合理评估，部分可获得良好预后；不需盲目终止妊娠。     

1075例产前诊断中32例染色体异常胎儿预后分析

目的探讨胎儿染色体异常与产前诊断的高危因素的关系及胎儿预后。方法回顾性分析2004年10月至2009年8月间在我院因各种原因行羊膜腔穿刺或脐带血穿刺产前诊断的胎儿染色体核型。结果总共1075例产前诊断中共发现胎儿染色体异常32人,染色体异常检出率2.97%。其中检出45,XY,t(21.14)1例,双胎均为46,XX,22Pstk+1例,47,XY,+(?),1例,46,XX,t(8;16)1例,46,XY,t(1;18)1例,46,XY,t(2;14)1例,46,XX,t(11;12)1例,产前诊断指征均为夫妻双方之一染色体平衡异位。46,XY,inv(Y)1例,产前诊断指征为生育过唐氏综合征。46,XY,inv(9)10例,产前诊断指征为羊水少,单脐动脉1人,孕期使用胚胎毒性药物使用史1人,唐氏征筛查高危4人,高龄2人,地中海贫血1人。47,XXY1例,产前诊断指征为胎儿双肾盂分离。唐氏综合征6例,产前诊断指征为唐氏征高危2人,高龄3人,NT值高1人。47,XYY2例,产前诊断指征为唐氏征高危1人,高龄1人。47,XXY/46,XX1例,产前诊断指征为唐氏征高危。18-三体3例,产前诊断指征为高龄1人,NT值高1人,18,13-三体高危1人。结论夫妻双方之一染色体平衡异位胎儿染色体核型异常类型多样。唐氏综合征及18-三体胎儿常见于高龄,血清学筛查高危,NT值升高孕妇。孕11-14周B超测NT值及孕中期血清学唐氏综合征筛查可以提高产前诊断的效率,减少出生缺陷。     

基于游离DNA单分子标签检测技术的眼皮肤白化病Ⅰ型的无创产前检测

目的:探讨基于游离DNA单分子标签检测技术(cfDNA barcode-enabled single-molecule test,cfBEST)的无创产前检测方法对于眼皮肤白化病Ⅰ型产前诊断的价值。方法:采用cfBEST方法为1个眼皮肤白化病Ⅰ型家系提供无创产前检测,之后通过羊膜腔穿刺产前诊断进行验证,并随访妊娠的结局...     

系统产前超声检查在胎儿先天性畸形中的应用

目的探讨中国医师协会超声医师分会公布的“产前超声检查指南”系统产前超声检查（Ⅲ级）胎儿畸形的应用价值,以此提高产前胎儿畸形的检出率。方法2912年10月至2014年2月间在我院接受胎儿系统检查的单胎孕妇521例。以“产前超声检查指南”为检查标准对胎儿进行系统超声检查：（1）对确诊的6大致死性胎儿畸形（产前诊断技术管理办法公布的无脑儿、脑膨出、开放性脊柱裂、胸腹壁缺损内脏外翻、单腔心及致死性软骨发育不全）建议临床终止妊娠;（2）对6大畸形以外的胎儿畸形进行跟踪随访;（3）对疑有染色体异常或难以确定的胎儿畸形病例进行转诊。结果521例单胎孕妇中检出致死性畸形5例（无脑儿I例,脑膨出2例,腹裂内脏外翻1例,单心室1例）,唇裂2例,唇腭裂1例,一侧肾积水2例,孤立性肾缺如1例,膈疝2例,肺囊腺瘤2例,单脐动脉2例,十二指肠闭锁2例,共计19例,其中漏诊和误诊各1例。结论“产前超声检查指南”临床应用,易于操作,遵循规范系统超声检查有利于提高胎儿畸形的检出率,避免漏诊率。     

孕妇产前诊断指征与胎儿染色体异常的关系

目的探讨产前诊断指征和产前诊断胎儿染色体异常间的关系。方法选择2018年6月至2018年12月于贵港市人民医院就诊的孕妇100例,收集所有孕妇产前诊断指征的资料,同时收集羊膜腔穿刺术检测胎儿染色体核型分析的结果。结果胎儿染色体异常共9例,总异常率占9.00%,其中无创基因检测异常组的胎儿染色体异常检出率为60.00%,明显高于高龄组的3.03%、唐氏筛查高危组的5.26%及胎儿超声异常组的7.69%,差异均有统计学意义(P<0.05);夫妇染色体异常组的胎儿染色体异常检出率为50.00%,明显高于高龄组,差异均有统计学意义(P<0.05);高龄组、唐氏筛查高危组、胎儿超声异常组间异常检出率无明显差异(P>0.05)。结论产前诊断指征与胎儿染色体异常密切相关,羊膜腔穿刺行染色体核型分析,能够有效检出胎儿染色体异常,对于有产前诊断指征的孕妇应尽早接受产前诊断,以降低新生儿出生缺陷的发生率。     

Fetal cells in transcervical samples at an early stage of gestation

Several investigations are in progress with the aim of performing prenatal diagnosis of inherited disorders by noninvasive or minimally invasive techniques. The most important approaches are based on the detection of fetal nucleated cells in maternal blood, the analysis of fetal DNA present in maternal plasma, and the identification and isolation of fetal trophoblastic cellular elements shed into the uterine cavity and the endocervical canal. In this review, we discuss the methods that have been employed for the collection of the transcervical samples at an early stage of gestation and the techniques used for the identification of fetal cells. We also report the results of using endocervical cells for the detection of fetal chromosomal disorders by fluorescent in-situ hybridization and for performing prenatal diagnosis of fetal Rh(D) phenotypes. Recent investigations have also shown that — after the isolation of trophoblastic cells from maternal contaminants by micromanipulation — transcervical samples can be employed for the prenatal diagnosis of single gene defects, such as those causing thalassemia and sickle cell anemia. Although the present results are promising, further investigations are required to demonstrate the feasibility of performing accurate diagnosis of fetal diseases by this minimally invasive approach in all transcervical samples retrieved at an early stage of gestation. Received: November 7, 2000 / Accepted: November 27, 2000     

"Blind" versus direct vision technique for fetal skin sampling in cases for prenatal diagnosis

Seven fetuses at risk of developing a serious inherited skin disorder (epidermolysis bullosa atrophicans generalisata gravis in 4, bullous ichthyosiform erythroderma in 2, and non-bullous ichthyosiform erythroderma in 1) were subjected to prenatal diagnosis by fetal skin sampling. The conventional "blind" biopsy procedure was used in the first 3 cases; a two-cannula technique (one cannula for the optic instrument and the other for the biopsy forceps) that permits biopsy of the skin under direct vision, was employed in the remaining 4 cases. With the "blind" technique, 8 to 10 biopsy specimens had to be taken to ensure that enough skin material would be available for the microscopic examination; only one specimen out of every two was found to consist of skin; the remainder comprised fetal membranes, myometrium, or tro-phoblast. In one case where the "blind" procedure had been used, leakage of amniotic fluid occurred and labor started in the 33rd week. With the two-cannula technique, the number of biopsy samples could be confined to two or three, and all proved to be of skin.