Correlation between rare chromosomal abnormalities and prenatal ultrasound findings

Our objective was to examine ultrasound findings with outcomes in cases of rare chromosomal abnormalities diagnosed during pregnancy. Results of cytogenetic studies obtained from amniocenteses and chorionic villus samplings (CVS) from 1994–2000 were reviewed. Only those examples of rare chromosomal abnormalities with little information on the associated outcome were included. Cases of autosomal trisomy (13, 18, and 21), sex chromosome aneuploidy, and reciprocal or Robertsonian translocations were excluded. Ultrasound findings and outcomes were reviewed. In all, 8,642 procedures of amniocenteses and 557 of CVS were performed; 21 cases met the inclusion criteria. Parental karyotypes were obtained for 19 couples and the karyotypic abnormalities were de novo in 13. Abnormal ultrasound findings were present in 14 pregnancies, with the following outcomes: seven underwent dilatation and evacuation (D&E), with abnormal findings in two (although examination was limited by fragmentation); one medical termination with micrognathia and low‐set ears; one fetal demise; one neonatal demise; three surviving neonates with abnormalities (one each with congenital kyphosis, hydronephrosis, and hypotonia), and one newborn was normal. There were seven patients without abnormal ultrasound findings with the following outcomes: three underwent D&E, with abnormal findings in two, one child with a colobomatous optic nerve, and two apparently normal infants. Follow‐up was not available in one patient. We conclude that when rare karyotypes and ultrasound abnormalities are present, poor outcomes are likely. Even with normal ultrasound findings, abnormalities may be present. These data may assist in counseling patients when testing reveals such chromosomal abnormalities. © 2002 Wiley‐Liss, Inc.     

妊娠孕妇产前超声检查胎儿心脏异常表现与染色体异常的相关性

目的探究妊娠孕妇产前超声检查胎儿心脏异常表现与染色体异常的相关性。方法回顾性分析我院2016年2月-2018年2月产前检查的500例胎儿心脏超声检查及染色体核型分析结果,分析心脏异常与染色体核型分析结果的相关性。结果本研究中共有26例发生胎儿心脏异常,37例存在染色体异常,26例胎儿心脏异常中共有19例发生染色体异常,发生率为73.08%。26例发生心脏异常的胎儿主要为室间隔缺损、卵圆孔未闭、三尖瓣轻度反流、左室功能异常,其中室间隔缺损发生率最高,其染色体异常率占总异常率的18.92%,三尖瓣轻度反流最低,占5.41%。将上述数据代入Spearman检验后发现,胎儿心脏异常表现与染色体异常成正相关(P<0.05)。结论妊娠孕妇产前超声检查胎儿心脏异常表现与染色体异常存在正相关,当胎儿出现心脏结构畸形时,胎儿染色体异常发生率较高,临床在超声检查应尤为注意。     

Correlation of placental pathology with prenatal ultrasound findings

There have been recent major advances in obstetric ultrasound, regarding both improved technologies and sonographer expertise, which have resulted in changes in antenatal obstetric management. The placenta is routinely examined to some extent at the time of the second trimester fetal anomaly sonogram, timing of delivery in pregnancies complicated by intrauterine growth restriction is primarily dependent on Doppler sonographic assessment of umbilical and uterine artery blood flow, and an increasing number of specific placental lesions have been described. Many non-specialist diagnostic histopathologists may be unfamiliar with these obstetric advances, but they are an increasingly common indication for submission of placentas for histological examination. Since the aims of pathological examination of the placenta are to determine the pathological basis for the clinical findings and advance understanding of the pathophysiology of pregnancy complications, this review therefore provides an overview of the most common prenatal sonographic techniques and their clinical relevance to the diagnostic pathologist, primarily focusing on conditions with specific placental implications. These range from abnormalities of placental site and cord insertion, to obstetric complications such as antepartum haemorrhage, through sonographic placental parenchymal lesions such as subchorionic and intervillous thrombi, or chorioangiomata. In addition, the pathophysiological basis of abnormal maternal and fetal maternal Doppler indices and intrauterine growth restriction are now described, being associated with decidual vasculopathy and villous changes associated with reduced intervillous blood flow respectively. Finally, rare but characteristic, sonographic appearances of villous cystic or hydropic change, may be associated with intrinsic developmental placental abnormalities such as hydatidiform mole and placental mesenchymal dysplasia, which require histological examination for their specific diagnosis.     

胎儿超声检查异常与染色体异常相关性研究

目的超声检查是评估胎儿染色体疾病的一种产前检查。本文主要研究目的是评估超声检查异常是否与胎儿染色体异常相关。方法对149例超声检查异常的胎儿行染色体核型检查和全基因组芯片检查。结果149例超声检查异常胎儿中,有32个染色体异常。其中数目异常有11例,多态性有9例,染色体微缺失或者微重复11例。结论产前超声检查发现异常的胎儿,应建议其通过羊膜腔穿刺术或脐血穿刺术进行传统的染色体核型分析或全基因组芯片排除染色体非整倍体或者结构异常。     

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。     

Correlation between centrosome abnormalities and chromosomal instability in human pancreatic cancer cells

Chromosomal instability, characterized by abnormal numbers or structures of chromosomes, is a common feature of human cancers, but the mechanisms behind these changes are still unclear. Since centrosomes play a pivotal role in balanced chromosomal segregation during mitosis, we attempted to investigate the association between centrosome abnormalities and chromosomal instability in a large number of human pancreatic cancer cell lines. Immunofluorescence microscopy revealed centrosomes that were highly atypical with respect to their size, shape, and number in most cell lines. These abnormal centrosomes contributed to the assembly of multipolar spindles, resulting in defective mitosis and chromosome mis-segregation. Interestingly, a high frequency of centrosome defects inversely correlated with the growth rate of cells in culture. Fluorescence in situ hybridization revealed a dramatic variation of chromosome numbers in cell lines with the defective centrosome phenotype. Furthermore, a significant positive correlation existed between the level of centrosome defects and the level of chromosomal imbalances. These results indicate that centrosome abnormalities can lead to spindle disorganization and chromosome segregation errors, which may drive the accumulation of chromosomal alterations. Thus, defects in centrosome function may be an underlying cause of genetic instability in human pancreatic cancers.     

超声软指标在染色体病产前筛查中的应用进展

染色体异常在新生儿的发病率约为0.1%~0.2%,其中唐氏综合征发病率最高。产前超声检查胎儿畸形伴染色体异常的价值已得到肯定,可以检查出包括21-三体、13-三体、18-三体、三倍体综合征和Turner综合征等染色体疾病。早孕或中孕期超声筛查出的2个及以上超声软指标异常,可更早提示胎儿染色体异常或结构畸形,这些软指标包括胎儿颈部皱褶、心室内强回声点、肠管强回声、脉络膜囊肿、轻度肾盂扩张、长骨短小等。本文将系统回顾常见的超声软指标,讨论其在染色体异常胎儿中风险评估价值、筛查技巧和测量标准,以期超声在产前诊断中获得更好的实用价值。     

Correlation between chromosomal abnormalities and blast phenotype in the blast crisis of Ph-positive CGL

We carried out cytogenetic analysis in 23 patients with Ph-positive chronic granulocytic leukemia in blast crisis. In all cases the type of blast cell was characterized by cytochemistry, immunologic markers, and ultrastructural studies. Twelve cases were classified as myeloid transformation, six as lymphoid, two as mixed (lymphoid and myeloid), and two were unclassifiable. Duplication of Ph was the most frequent abnormality in the whole series. Trisomy 8, i(17q) and trisomy 19 were seen only in patients with myeloid blast crisis (53%, 30%, and 23%, respectively). Our findings suggest that the nature of additional chromosome abnormalities arising in blasts with features of myeloid differentiation are different from those in blasts showing lymphoid differentiation.     

Prenatal detection of rare chromosomal autosomal abnormalities in Europe

The aim of the present study was to evaluate the prenatal detection of rare chromosomal autosomal abnormalities by ultrasound (US) examination. Data were obtained from 19 congenital malformation registries from 11 European countries, between 01/07/96 and 31/12/98. A total of 664,340 births were covered and 7,758 cases with congenital malformations were recorded. Rare autosomal abnormalities were diagnosed in 114 cases (6.6%) from a total of 1,738 chromosome abnormalities. There were a wide variety of autosomal abnormalities: the most common were deletions (33 cases), duplications (32 cases), trisomies of chromosomes 8, 9, 10, 14, 15, and 16 (23 cases), and unbalanced rearrangements (19 cases). Out of these cases, 45.6% were detected prenatally by US examination due to the presence of congenital anomaly. As for the types of chromosomal anomaly, unbalanced rearrangements and deletions were the most frequently detected by US. A high percentage of cases with balanced rearrangements were associated with severe congenital anomalies. The most frequent congenital anomalies detected by US were cystic hygroma (20.6%), central nervous system defects (17.6%), cardiac defects (13.2%), and diaphragm defects (10.3%). This large series offers useful information about prenatal diagnosis by US of congenital defects associated with rare autosomal abnormalities and it provides a valuable knowledge about outcome. Fetal anomalies detected by US that were associated with rare autosomal abnormalities were significantly more frequent than those associated with common chromosomal abnormalities (45.6 vs. 34.7%). This study indicates the need to increase the detection of congenital anomalies by US.     

荧光原位杂交技术在胎儿染色体异常产前诊断中的应用

目的探讨荧光原位杂交(FISH)技术在检测胎儿染色体异常的临床应用。方法选用13、21、18、X、Y特异性探针对1128例孕16～22周有产前诊断指征的妊娠妇女羊水间期细胞进行分析,并与同时进行的羊水细胞培养核型分析结果进行对照。结果被检1128例羊水间期细胞FISH检测均成功,其中检出正常核型1081例,数目异常核型20例,与常规细胞染色体核型分析结果一致,另外27例结构异常FISH技术未能检出。结论 FISH技术检测胎儿染色体数目异常具有快速、简便、准确性高、特异性强等优点,有较大的临床应用价值,并对产前细胞遗传学诊断有重要意义。     

胎儿结构畸形、微小畸形与染色体异常的相关性研究

目的通过对不同类型和数量的胎儿结构畸形、微小畸形与染色体异常的关系性研究,从而对具有上述病变的胎儿的遗传咨询和染色体产前诊断做一个更好的指引。方法收集2004年1月至2005年12月因发现胎儿结构畸形和微小畸形于孕中晚期进行脐带穿刺术及染色体检查病例120例。统计不同的结构畸形、微小畸形的染色体异常核型的检出率、检出类型。并对所有病例进行术后或出生后随访。结果脐带穿刺术和脐血染色体培养成功率为100%,检出异常核型13例(10.8%)。其中18三体异常核型6例,21三体2例,13三体1例,45,XO(Turner综合征)1例,衍生染色体2例,嵌合体1例。多发畸形染色体异常发生率为40%(8/20);单发畸形染色体异常发生率为7.3%(3/41);单独存在的胎儿超声软指标染色体异常发生率为2.1%(1/47);多个超声软指标染色体异常发生率为8.3%(1/12)。结论胎儿结构畸形与非整倍体染色体病关系密切,而单独存在的超声软指标发生染色体异常的机率较低,但当出现2个以上软指标时发生染色体异常的几率将增加。我们应根据结构异常的种类和数量,给予孕妇不同的产前咨询意见和提供必要的侵入性检查。     

Application of chromosomal microarray in the evaluation of abnormal prenatal findings

We performed karyotype and array comparative genomic hybridization (aCGH) analyses on 177 prenatal samples, including 162 (92%) samples from fetuses with sonographic anomalies. Overall 12 fetuses (6.8%) had abnormal karyotype and 42 (23.7%) fetuses had abnormal microarray results: 20 (11.3%) with pathogenic copy number variations (CNVs), 16 with CNVs of uncertain clinical significance, 4 with CNVs establishing carrier status for recessive, X‐linked, or susceptibility to late onset dominant disease, and two CNVs with pseudomosaicism due to in vitro cultural artifacts. For 23 pregnancies (13%), aCGH contributed important new information. Our results highlight the interpretation challenges associated with CNVs of unclear significance, incidental findings, as well as technical aspects. Array CGH analysis significantly improved the detection of genomic imbalances in prenatal diagnosis of pregnancies with structural birth defects.     

评价羊水染色体检测在产前诊断中的作用

目的评价羊水细胞染色体检测在产前诊断中的作用。方法对妊娠16∽24w的孕妇939例进行羊膜腔穿刺术,对羊水细胞染色体分析。结果检测出染色体异常共54例,其中21-三体13例,18-三体1例,13-三体1例,性染色体异常9例,平衡易位14例,其他染色体结构异常16例。结论羊水染色体检测可安全、有效的检测胎儿染色体异常,具有重要意义,值得进一步推广。     

荧光原位杂交技术在复杂染色体异常产前诊断中的应用

目的 探讨荧光原位杂交技术(fluorescence in situ hybridization,FISH)在复杂染色体异常产前诊断中的应用价值.方法 对8例羊水、3例脐血常规G显带具有复杂染色体异常的产前诊断孕妇,应用FISH技术确定其复杂染色体重排及标记染色体的组成.结果 FISH技术证实了G-显带平衡易位的结果,同时明确了3例羊水中衍生染色体的组成、2例脐血中标记染色体的来源.结论 FISH技术具很高的敏感性和特异性,是明确染色体异常重要的分子细胞遗传学工具,其在产前诊断中的应用,可为临床提供更准确全面的实验依据.     

Low doses of pulsed ultrasound and chromosomal abnormalities in male mouse germ cells

Male mice were exposed to pulsed ultrasound (intensity <1mW, frequency 3.5 MHz) for 30 min or to sham treatment. After30 h, 11, 12 or 13 days, the testes were cytologically and histologicallyexamined (using squash preparations, air-drying and sections).The resulting damage was studied at diakinesis—metaphaseI and II, spermatogonial metaphase and anaphase. The investigationby air-drying did not show any significant increase in chromosomedamage, 30 h, 11, 12 and 13 days after treatment (spermatogonialand spermatocytic metaphases). There was, however, a significantincrease of the frequency of aneuploid cells detected at metaphaseII. Investigations by squash techniques or sections did notreveal adverse effects on the spindles at spermatogonial andspermatocytic anaphases. We suggest that the reduction of fertilitypreviously observed in our clinic could be explained by an increaseof aneuploidy if germ cells are exposed to ultrasound duringdiakinesis of the first meiotic division.     

Frequencies of fetal chromosomal abnormalities at prenatal diagnosis: 10 years experiences in a single institution.

We present frequencies of fetal chromosomal abnormalities in 4,907 prenatal cytogenetic examinations at Samsung Cheil Hospital from 1988 to 1997 for 10 yr duration. Prenatal karyotypes were undertaken in 3,913 amniotic fluid samples, 800 chorionic villi samples, and 194 percutaneous umbilical blood samples. The frequency of fetal abnormal karyotypes was 3.1% (150 cases). Numerical chromosome abnormalities were 87 cases (1.8%) and structural aberrations of chromosomes were 63 cases (1.3%). In the numerical chromosomal abnormalities, the frequency of trisomy 21 was by far the highest (36 cases), followed by trisomy 18 in 22 cases and sex chromosome aneuploidies in 19 cases. In the structural chromosomal aberrations, 5 cases had the inversions in chromosome 2, 7, 17, and Y. Chromosomal deletions in 6 cases and additions in 4 cases were analysed. Of the remaining 47 translocation in abnormal fetuses, reciprocal translocation was in 26 cases and Robertsonian translocation in 21 cases. Among them, 41 cases were balanced translocation and 6 were unbalanced. Thirty five cases of translocation were inherited from one of the parents. Four had de novo chromosome rearrangements, and 8 cases were unknown.     

Fetal ultrasound abnormalities: Correlation with fetal karyotype,autopsy findings,and postnatal outcome—five-year prospective study

A 5-year prospective prenatal study in 151 pregnancies with 152 malformed fetuses detected by ultrasound was evaluated cytogenetically. Thirty-five fetuses (23%) had abnormal karyotypes. Specific anatomical fetal malformations identified by ultrasound increase the risk for fetal chromosome abnormalities. Risks of abnormal chromosomes in the fetus are present with both single and multiple anomalies including amniotic fluid volume although the risk is increased with specific anatomical systems and multiple malformations. An abnormal fetal karyotype was present in 17% with a single anatomical abnormality and 30% when two or more anatomical systems were involved. Fetal hydrops, duodenal atresia, and omphalocele were the most specific single ultrasound anomalies; fetal hydrops, IUGR, holoprosencephaly, congenital heart disease, diaphragmatic hernia, duodenal atresia, and omphalocele were the most specific multiple anomalies with abnormal amniotic fluid volume. Termination of pregnancy occurred in 32/58 patients diagnosed prior to the 20th week of pregnancy with most (31/32) having a chromosomal anomaly or severe fetal anomaly. Fetuses terminated after the 20th week had chromosomal (7/18) or lethal fetal anomalies (11/18). The most common aneuploidies were trisomy 21, trisomy 18, and 45,X. The decision to terminate the pregnancy was based in most cases on the fetal ultrasound findings. Correlation of ultrasound and clinical findings is important for accurate genetic counselling. © 1992 Wiley-Liss, Inc.     

QF-PCR技术在胎儿超声异常病例快速产前诊断中的应用研究

目的探讨分析荧光定量PCR(Quantitative Fluorescent Polymerase Chain Reaction,QF-PCR)技术在快速产前诊断常见染色体非整倍体中的临床应用价值。方法用QF-PCR技术和核型分析两种方法对180例产前诊断样本进行检测,比较结果。结果核型分析:共有175例产前诊断样本成功进行细胞培养,核型分析报告在2-3周发出;其中正常133例,异常42例。QF-PCR结果:所有样本均成功在48h内进行QF-PCR检测;共检出染色体数目正常145例,异常35例,其中核型分析检测到的10例21-三体、13例18-三体、4例13-三体、5例45,X、1例三倍体用QF-PCR方法全部检出,1例46,XY,der(14;21)(q10;q10)和1例46,XX,der(14;21)(q10;q10),QF-PCR检测结果为21-三体。QF-PCR技术对五种常见染色体非整倍体的检出率为100%,无假阳性。结论 QF-PCR技术能够在48h内快速、准确地诊断21、18、13、X及Y染色体非整倍体,此技术在快速产前诊断常见非整倍体方面具有重要临床实用价值。     

染色体异常与疾病之间关系的临床分析

目的研究染色体异常与临床疾病发生之间的关系。方法采用人外周血淋巴细胞培养，常规G显带技术进行核型分析。结果298例检查者中，染色体异常59例，染色体检出率18．8％。染色体异常疾病主要发生于有不良妊娠史、男性少弱精症、男女性发育异常及智力低下。在59例染色体异常中，数目异常占20．34％，嵌舍体占5．08％，结构异常占20．34％，染色体多态性占49．15％。有3例社会性别为女性，染色体核型为男性。结论染色体异常会导致临床疾病的发生，遗传咨询和产前诊断对染色体异常疾病有预防作用。     

Correlation between poliomyelitisvirus-reproduction-cycle,chromosomal alterations and lysosomal enzymes

Summary Complete poliovirus reproduction-cycle in human aneuploid tissue culture cells causes chromosomal damage and increase of non-particulate lysosomal enzymes. — Guanidine-inhibition of late stages of infection gives evidence that breakage and c-anaphase-like chromosomes are independent of the complete reproduction-cycle. Severe diffuse chromoomal alterations, however, and increase of lysosomal enzymes require late stages of infection. — In this host-virus-system lysosomal enzymes are not responsible for incidence of chromosomal breakage and c-anaphaselike figures. The role of lysosomal enzymes for severe diffuse chromosomal alterations is still in question.