High-grade serous carcinoma of the fallopian tube in a young woman with chromosomal 4q abnormality:A case report

BACKGROUND Few studies have reported an association between an increased risk of acquiring cancers and survival in patients with 4q deletion syndrome.This study presents a rare association between chromosome 4q abnormalities and fallopian tube highgrade serous carcinoma(HGSC)in a young woman.CASE SUMMARY A 35-year-old woman presented with acute dull abdominal pain and a known chromosomal abnormality involving 4q13.3 duplication and 4q23q24 deletion.Upon arrival at the emergency room,her abdomen appeared ovoid and distended with palpable shifting dullness.Ascites were identified through abdominal ultrasound,and computed tomography revealed an omentum cake and an enlarged bilateral adnexa.Blood tests showed elevated CA-125 levels.Paracentesis was conducted,and immunohistochemistry indicated that the cancer cells favored an ovarian origin,making us suspect ovarian cancer.The patient underwent debulking surgery,which led to a diagnosis of stage IIIC HGSC of the fallopian tube.Subsequently,the patient received adjuvant chemotherapy with carboplatin and paclitaxel,resulting in stable current condition.CONCLUSION This study demonstrates a rare correlation between a chromosome 4q abnormality and HGSC.UBE2D3 may affect crucial cancer-related pathways,including P53,BRCA,cyclin D,and tyrosine kinase receptors,thereby possibly contributing to cancer development.In addition,ADH1 and DDIT4 may be potential influencers of both carcinogenic and therapeutic responses.

Embryo quality and chromosomal abnormality in embryos from couples undergoing assisted reproductive technology using preimplantation genetic screening

Objective:To detect common chromosomal aneuploidy variations in embryos from couples undergoing assisted reproductive technology and preimplantation genetic screening and their possible associations with embryo quality.Methods:In this study,359 embryos from 62 couples were screened for chromosomes 13,21,18,X,and Y by fluorescence insitu hybridization.For biopsy of blastomere,a laser was used to remove a significantly smaller portion of the zona pellucida.One blastomere was gently biopsied by an aspiration pipette through the hole.After biopsy,the embryo was immediately returned to the embryo scope until transfer.Embryo integrity and blastocyst formation were assessed on day 5.Results:Totally,282 embryos from 62 couples were evaluated.The chromosomes were normal in 199(70.57%)embryos and abnormal in 83(29.43%)embryos.There was no significant association between the quality of embryos and numerical chromosomal abnormality(P=0.67).Conclusions:Embryo quality is not significantly correlated with its genetic status.Hence,the quality of embryos determined by morphological parameters is not an appropriate method for choosing embryos without these abnormalities.

Correlation between Reasons for Prescription and Karyotype Results in Patients Referred for Suspected Chromosomal Abnormalities

Karyotype prescription is based on clinical signs (or reasons for karyotype prescription) which are phenotypic manifestations associated with chromosomal abnormalities. The aim of this study was to establish a correspondence between karyotype indications and their results in patients. This was a retrospective study that was carried out in the Histology-Embryology-Cytogenetics laboratory of the University Hospital of Cocody-Abidjan from 2014 to 2019. 58 patient files were identified and included the indication or reason for prescribing a constitutional karyotype and the biological result obtained. An individual data sheet was used to collect the data. 17 reasons for prescription were identified and divided into 2 groups. Sexual ambiguity was the most frequent reason (29.3%). The first group (G1) represented the 10 reasons for which the karyotype results were normal. The second group (G2) corresponded of the 7 motives with normal or abnormal karyotype results. Several anomalies were listed according to these reasons: inversions, mosaics (anomalies of number and structure) and trisomy 21. The last was the most frequent chromosomal anomaly (69.24%). It was found in several reasons for karyotype prescription: malformations, neurological disorders, suspected trisomy and cardiac pathology. Several factors could explain these results, among which are the limits of the karyotype and the non-genetic causes that can induce these abnormal phenotypes. Complementary examinations to the karyotype are molecular cytogenetic techniques, notably fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (Array-CGH).

Identification of embryonic chromosomal abnormality using FISH-based preimplantaion genetic diagnosis

Objective: Embryonic chromosomal abnormality is one of the main reasons for in vitro fertilization (IVF) failure. This study aimed at evaluating the value of Fluorescence in-situ Hybridization (FISH)-based Preimplantation Genetic Diagnosis (PGD) in screening for embryonic chromosomal abnormality to increase the successful rate of IVF. Method: Ten couples, four with high risk of chromosomal abnormality and six infertile couples, underwent FISH-based PGD during IVF procedure. At day 3, one or two blastomeres were aspirated from each embryo. Biopsied blastomeres were examined using FISH analysis to screen out embryos with chromosomal abnormalities. At day 4, embryos without detectable chromosomal abnormality were transferred to the mother bodies as in regular IVF. Results: Among 54 embryos screened using FISH-based PGD, 30 embryos were detected to have chromosomal abnormalities. The 24 healthy embryos were implanted, resulting in four clinical pregnancies, two of which led to successful normal birth of two healthy babies; one to ongoing pregnancy during the writing of this article; and one to ectopic pregnancy. Conclusion: FISH-based PGD is an effective method for detecting embryonic chromosomal abnormality, which is one of the common causes of spontaneous miscarriages and chromosomally unbalanced offsprings.

Rapid Diagnosis with FISH for Chromosomal Abnormality of Fetal Pyelectasia

Fluorescence in situ Hybridization （FISH） was used to investigate whether the chromosome of the fetus prenatally diagnosed as pyelectasis was normal or not. Amniotic fluid was taken from the pregnant woman whose fetus was detected with pyelectasia by prenatal examination. The chromosome of the amniotic fluid cell without culture was examined with FISH. The result shows that compared with the traditional amniotic fluid cell culture, FISH has the advantages of more rapid, higher sensitivity and specificity, and was 10-12 days earlier to complete the diagnosing than the traditional method. The fetuses detected chromosomal abnormality in each groups were induced during the middle and late trimester, while those fetuses with normal chromosome continued pregnancy, the rate of spontaneous disappearance of pyelectasia decreased as the severity of pyelectasia increased. FISH can satisfy the urgent need in the clinical prenatal diagnosis due to its rapidity to determine whether fetus with pyelectasia was accompanied with chromosomal.

High Expression of hsMAD2 in the Villi of Spontaneously Aborted Embryo with Chromosomal Abnormality

Objective: To investigate the changes of hsMAD2 protein and gene expression levels during chromosome segregation of human embryos. Method: The embryos of spontaneous abortion were collected in our hospital from 2009 to 2013, the chromosomal numbers of the embryonic villi were subsequently detected by fluorescence in situ hybridization (FISH). The patients were then divided into the normal and abnormal groups based on the chromosome number. The hsMAD2 protein and gene expression levels in the villi tissues of the two embryo groups were detected by western blotting and qRT-PCR, respectively. The hsMAD2 protein and gene levels in the embryonic villus tissue of the patient were detected. Results: From 2009 to 2013, we collected 50 embryos from spontaneous abortion patients. The chromosome abnormality and no abnormality were 36 cases (abnormal number of 28 cases (56.0%) and chimerism in 8 cases (16.0%)) and 14 cases (28.0%), respectively. The expression of hsmad2 protein and its gene in the villi of spontaneously aborted embryo with chromosomal abnormality in the abnormal group was significantly higher than that in those without chromosomal abnormalities (0.88 ± 0.20 vs 0.61 ± 0.19, P < 0.05), (23.46 ± 0.07 vs 18.35 ± 0.10, P < 0.05). Conclusion: Abnormal number of chromosomes is closely related to spontaneous abortion Linked, hsMAD2 factor has a card effect on the cell cycle, can block the mitotic process of cells, and play an important role in maintaining the normal separation and stability of chromosomes.

Instrument-Dependent or Instrument-Independent Indications and Prevalence of Chromosomal Abnormalities by Amniocentesis in China:An Analysis of 4146 Cases of Amniocentesis

Objective:There is a high incidence of birth defects in China,and prenatal diagnosis is an important method of intervention.This study aims to describe the clinical indications and cytogenetic results of amniocentesis cases in central China.Methods:We retrospectively reviewed cases at the Maternal and Child Care Service Centre in Henan Province from January 2012 to December 2014.A total of 4497 at-risk mothers(risk factors:advanced maternal age,history of intrauterine fetal death or aborted fetuses,chromosomal abnormality in one of the parents,high-risk maternal serum screening results,and abnormal ultrasonographic findings in the first or second trimester)were recruited for amniocentesis(AS).The subjects included were between 11–14 and 18–22 weeks of gestation.All cases were divided into two groups based on instrument-independent or instrument-dependent indications.Results:A total of 4146 cases were analyzed.Of these,chromosomal abnormalities were detected in 232 cases(5.6%),and autosomal aneuploidy,including trisomy 21 and trisomy 18,was found to be the most common(55.7%)chromosomal abnormality.The mean age of 29.94 years was not expected as all mothers older than 35 years old were routinely offered amniocentesis at the time of the study.Amniocentesis was carried out in 1711 cases because of instrument-independent indications,and 285 of these cases were diagnosed with chromosomal abnormality.In 2376 cases,amniocentesis was conducted because of instrumentdependent indications,and 176 of these were diagnosed with chromosomal abnormality.Thus,5.6%of the cases were diagnosed with chromosomal abnormalities,and autosomal aneuploidy,including trisomy 21 and trisomy 18,were the most common chromosomal abnormalities detected in the present study Conclusion:Our result indicated the significance of instrument-independent indications in the screening of chromosomal abnormalities,especially in developing areas.Birth defects may be reduced by paying more attention to the patients’history of medication.

FISH studies of chromosome abnormalities in germ cells and its relevance in reproductive counseling

Chromosome abnormalities are one of the major causes of human infertility. In infertile males, abnormal karyotypes are more frequent than in the general population. Furthermore, meiotic disorders affecting the germ cell-line have been observed in men with normal somatic karyotypes consulting for infertility. In both cases, the production of unbalanced spermatozoa has been demonstrated. Basically addressed to establish reproductive risks, fluorescence in situ hybridization （FISH） on decondensed sperm heads has become the most frequently used method to evaluate the chromosomal constitution of spermatozoa in carriers of numerical sex chromosome abnormalities, carriers of structural chromosome reorganizations and infertile males with normal karyotype. The aim of this review is to present updated figures of the information obtained through sperm FISH studies with an emphasis on its clinical significance. Furthermore, the incorporation of novel FISH-based techniques （Multiplex-FISH; Multi-FISH） in male infertility studies is also discussed. （Asian J Androl 2005 Sep; 7： 227-236）

Application of dual color fluorescence in situ hybridiza tion (D-FISH) to the diagnosis of a 49, XXXXY chromo somal abnormality

To study the technique of D-FISH and its application in the diagnosis of a 49, XXXXY chromosomal abnormality. Methods: Biotin-labeled alpha satellite X chromosome DNA (pBamX7) probe and digoxi-genin-labeled Y chromosome long arm terminal repetitive sequence (pY3.4) probe in situ hybridized with pre-treated slides of peripheral blood chromosome and interphase nucleus. After washing, the slides were treated with avidin-FITC, rhodamine-FITC and anti-avidin, amplified with an additional layer and counter-stained with DAPI in an antifade solution. The hy bridization signals and chromosomal or interphase nucleus settings were observed respectively with WIB, WIG and WU filters under fluorescent microscope (Olympus AX-70) and the number of metaphase chromosome and interphase nucleus in the peripheral blood was counted. Results: The biotin-labeled pBamX7 probe showed 4 green hybridization signal and the digoxigenin-labeled pY3.4 probe showed 1 red hybridization signal. The chromosome or cytoplasm counter-stained with DAPI showed blue. The positive rate of X chromosome hybridization signal for the 350 metaphase chromosomes and interphase nucleus was 91.43 % and 92. 57 %, respectively, while that of the Y chromosome hybridization signal was 99.5 % and 99.8 %, respectively. Conclusion: D-FISH is a valuable technique in diagnosing 49, XXXXY chromosomal abnormality and other sex chromosomal abnormalities. [Reprod Contracep (in Chinese) 2002; 22: 287]

Unusual cytogenetic abnormalities associated with Philadelphia chromosome

Cytogenetic abnormalities are the hallmark of leukemias. We report here two cases of unusual cytogenetic abnormalities associated with Philadelphia chromosome, one with mixed phenotypic acute leukemia showing monosomy 7 and t(9;22)(q34;q11.2) and the other with chronic myeloid leukemia and additional translocation involving chromosomes 10 and 13. Both patients achieved complete remission following imatinib based treatment.

Recurrent isochromosome 21 and multiple abnormalities in a patient suspected of having acute myeloid leukemia with eosinophilic differentiation—a rare case from South India

Acute myeloid leukemia (AML) is a phenotypically heterogeneous disorder. The M4 subtype of AML is frequently associated with the cytogenetic marker inversion 16 and/or the presence of eosinophilia. Blast crisis is the aggressive phase of the triphasic chronic myeloid leukemia (CML), which is a disease with Philadelphia (Ph) chromosome as the major abnormality. In the present study, we report a 76-year-old patient suspected of having AML with eosinophilic differentiation (AML-M4), which in clinical tests resembles CML blast crisis with multiple chromosomal abnormalities. Isochromosome 21 [i(21)(q10)] was the most recurrent feature noted in metaphases with 46 chromosomes. Ring chromosome, tetraploid endoreduplication, recurrent aneuploid clones with loss of X chromosome, monosomy 17, monosomy 7, and structural variation translocation (9;14) were also observed in this patient. Fluorescent in situ hybridization (FISH) confirmed the absence of Ph chromosome. This report shows how cytogenetic analyses revealed atypical structural aberrations in the M4 subtype of AML.

45,X/47,XYY性发育异常一例并文献复习

45,X/47,XYY性发育异常是一种由于罕见的染色体异常导致的性发育异常疾病。报告1例收治的45,X/47,XYY嵌合型性发育异常患者,该患者主因原发性闭经并出现男性化表现就诊,具有特纳综合征(Turner syndrome,Turner综合征)的表现,腹腔镜探查显示一侧性腺为条索状,另一侧外观睾丸样,病理为卵睾型性腺,手术切除双侧附件并予人工周期治疗,有月经来潮。结合本例及检索到的文献报道的女性表型中因原发性闭经就诊的病例共11例,对该病的临床表现、诊断及治疗方式进行总结。女性表型45,X/47,XYY性发育异常患者临床表现多样,以Turner综合征表现合并男性化表现多见,应尽早发现并切除发育不良的性腺,防止性腺肿瘤的发生和男性化表现出现。术后进行长期激素替代治疗,同时注重患者精神心理的疏导。

超声评估颈项透明层厚度增厚和鼻骨钙化不良结合染色体微阵列分析在胎儿产前诊断中的应用

目的探讨染色体微阵列分析(chromosomal microarray analysis,CMA)在颈项透明层厚度(Nuchal translucency,NT)增厚和鼻骨钙化不良胎儿产前诊断中的应用价值。方法选择2022年9月至2024年4月期间在本院产前诊断中心诊断为NT增厚和/或鼻骨钙化不良并接受了CMA、染色体核型分析的75例胎儿进行研究,分析NT增厚和鼻骨钙化不良与染色体异常的关系、CMA对NT增厚和鼻骨钙化不良胎儿的染色体异常检出情况,以及超声联合CMA在产前诊断中的价值。结果75例NT增厚和/或鼻骨钙化不良的胎儿中,核型分析检出染色体非整倍体11例,CMA额外检出致病性拷贝数目变异(Copy number variations,CNV)5例,额外检出率为6.7%。单纯NT增厚、鼻骨钙化不良胎儿的CMA额外诊断率分别为6.0%、5.0%。结论CMA技术在NT增厚和鼻骨钙化不良胎儿的产前诊断中的价值较高,能够提高胎儿染色体异常的检出率,多种技术的联合应用可为胎儿提供更全面的评估。

884例性染色体异常胎儿产前诊断结果分析

目的 对884例无创产前筛查(NIPS)提示性染色体异常的羊水样本进行核型分析、荧光原位杂交技术(FISH)和拷贝数变异测序(CNV-seq)检测,探讨不同方法在产前诊断中的价值。方法 选取2015年1月—2022年12月天津市中心妇产科医院孕早期NIPS提示胎儿为性染色体异常的孕妇884例,于孕中期采集羊水样本,进行羊水细胞核型分析和FISH检测,对结果不一致或培养失败的样本进一步行CNV-seq检测。结果 884例孕妇中,有341例(38.6%)检出异常核型,11例(1.2%)羊水细胞培养失败。NIPS性染色体阳性预测值为39.2%(341/873)。341例核型分析异常样本中,最常见的核型异常类型是47,XXY(108例),其次为47,XXX(80例)、47,XYY(68例)、45,X(18例),共检出51例嵌合体。884例孕妇中,有862例FISH检测结果与核型分析或CNV-seq结果一致,FISH的阳性预测值为97.5%;24例与核型分析结果不一致,进一步行CNV-seq检测,有22例CNV-seq结果与核型分析结果一致,并能相互补充分析;2例不一致样本中,1例核型分析结果为46,~+mar,FISH和CNV-seq结果均为45,X;1例核型分析结果为嵌合Y染色体异染色质区缺失,FISH和CNV-seq结果均为嵌合体,结构未见异常。结论 NIPS提示性染色体异常时,建议首选FISH和核型分析联合检测,可快速、准确地诊断染色体异常。对于疑似染色体特殊结构异常,建议进行FISH、核型分析和CNV-seq联合检测,可明确遗传学病因。

388例骨骼发育异常胎儿遗传学分析

目的分析骨骼发育异常胎儿的遗传学因素,探讨其在骨骼发育异常胎儿中的作用。方法选择2016年1月至2022年12月于广西壮族自治区妇幼保健院进行产前检查的388例超声检查提示骨骼发育异常或合并其他结构异常的胎儿为研究对象。回顾性分析388例胎儿的临床资料,比较其染色体核型分析与单核苷酸多态性微阵列(SNP-array)的检测结果。结果388例胎儿骨骼发育异常产前样本中,染色体核型分析结果发现异常20例,异常检出率为5.2%(20/388);SNP-array检出异常56例,异常检出率为14.4%(56/388)。在SNP-array检出的56例异常胎儿中,有19例胎儿的染色体核型分析结果为异常,其余37例胎儿核型正常。这37例正常核型胎儿中有12例为致病性拷贝数变异(CNVs),检出率为3.1%(12/388);另外25例为临床意义不明性CNVs。结论当超声检查提示胎儿骨骼发育异常时,胎儿可能存在染色体异常,建议行介入性产前诊断,以明确胎儿是否存在致病性基因缺陷,为临床遗传咨询提供更多参考依据。

超声联合染色体检测在诊断胎儿心脏发育异常中的价值

目的本研究旨在探讨超声联合染色体检测对于诊断胎儿心脏发育异常的临床价值。方法前瞻性选取2022年1月至2022年12月在上海交通大学医学院附属国际和平妇幼保健院进行建档产检的孕妇进行超声检查,将高度疑似胎儿发育异常的96例孕妇纳入研究中。均接受染色体检测,以分娩后新生儿结局或引产诊断结果为金标准,对超声及染色体检测的诊断价值进行探究。结果对纳入研究的96例孕妇进行追踪随访(至分娩完成新生儿接受超声诊断或引产后接受病理诊断止),共追踪到29例胎儿心脏发育表现正常,67例胎儿心脏发育异常。经超声检查,32例产妇未见胎儿心脏发育异常,其他64例诊出胎儿心脏发育异常;经染色体检查,共诊出正常染色体36例,染色体异常64例。以分娩后新生儿结局或引产病理诊断结果为诊断金标准,超声检查真阳性(心脏发育异常)59例,真阴性(心脏发育异常)24例,超声联合染色体检测真阳性(心脏发育异常)63例,真阴性(心脏发育异常)23例。超声联合染色体检测诊断胎儿心脏发育异常的灵敏度、准确率分别为94.03%、89.58%,分别高于单独的超声检查(88.06%、86.46%),AUC值(95%CI)为0.854(0.762~0.946),优于单独的超声检查[0.878(0.773~0.960)]。结论超声联合染色体检测在诊断胎儿心脏发育异常方面具有较高的诊断价值和临床应用前景。相较于单独的超声检查,超声联合染色体检测展现出更高的灵敏度以及更优的准确率,可作为诊断胎儿心脏发育异常的有力工具。

1695例不同程度少精子症、无精子症患者的染色体遗传学差异分析

目的分析不同程度少精子症、无精子症患者的染色体遗传学特征,探讨染色体核型分析及Y染色体微缺失检查与少精子症、无精子症严重程度及男性不育的关系。方法选取2018年1月至2023年12月首都医科大学附属北京妇产医院收治的1695例少精子症、无精子症男性患者作为研究对象,抽取外周血进行高分辨染色体核型分析,其中590例中度、重度、极度少精子症及无精子症患者同时筛查Y染色体微缺失。结果1695例筛查染色体核型异常355例,占22.36%;其中染色体结构异常44例,数目异常22例,多态性289例。590例中度、重度、极度少精子症及无精子症患者Y染色体微缺失17例(2.88%)。138例无精子症中克氏征11例(7.97%),Y染色体微缺失17例(12.32%)。结论少精子症、无精子症患者出现染色体异常比例高于一般人群。少精子症、无精子症的发生可能与某些常见的染色体核型多态性相关;随着测序技术的展开,基因病可能是少精子症、无精子症的第一遗传因素。

超声检查联合NIPT在高龄孕妇产前筛查中的应用价值

目的探讨超声检查联合无创产前DNA检测(NIPT)在高龄孕妇中对胎儿染色体异常筛查的临床应用价值。方法选取2020-2023年在宝鸡市妇幼保健院接受产前检查的3820例高龄孕妇作为研究对象,所有孕妇均接受超声检查及NIPT,以羊膜腔穿刺结果或妊娠结局作为胎儿染色体异常的诊断标准,比较超声检查、NIPT及二者联合应用对胎儿染色体异常的诊断情况。结果3820例高龄孕妇中NIPT筛查出高风险57例;超声检查软指标异常95例,结构异常63例;超声检查联合NIPT诊断胎儿染色体异常的灵敏度、特异度和阳性预测值分别为93.18%、99.89%、91.11%。结论高龄孕妇胎儿染色体产前筛查中,超声检查联合NIPT可以相互补充参考,可有效提高染色体异常检出的灵敏度、特异度,降低假阳性率和假阴性率,实现对出生缺陷的早发现、早诊断及早干预。

超声测量前额空间比联合无创产前DNA筛查早孕期胎儿染色体异常的临床价值

目的应用超声测量前额空间比(PFSR),探讨其联合无创产前DNA检测(NIPT)在早孕期胎儿染色体异常筛查中的临床应用价值。方法选取在我院接受早孕期羊水穿刺染色体核型检测的高危孕妇80例,均行产前超声检查及NIPT,以羊水穿刺染色体核型检测结果为金标准,比较超声测量PFSR、NIPT及两者联合应用筛查早孕期胎儿染色体异常的诊断效能。结果80例高危孕妇中,羊水穿刺染色体核型检测筛查胎儿染色体异常11例,其中21-三体综合征6例,18-三体综合征2例,13-三体综合征2例,Turner综合征1例。超声测量PFSR筛查早孕期胎儿染色体异常的灵敏度、特异度及准确率分别为63.64%、86.96%、83.75%;NIPT的灵敏度、特异度及准确率分别为72.73%、88.41%、86.25%;两者联合应用的灵敏度、特异度及准确率分别为90.91%、98.55%、97.50%,均高于单一方法,差异均有统计学意义(均P<0.05)。结论超声测量PFSR联合NIPT能提高筛查早孕期胎儿染色体异常的诊断效能,具有较好的临床应用价值。