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.

A DiGeorge Syndrome Case Report—Challenges of Diagnosis and Management

Background: DiGeorge syndrome (also known as velo-cardio-facial syndrome) is a rare multisystem genetic disorder occurring in approximately 1 in 4000 to 1 in 6000 live births [1]. Although advances in genetic screening have improved diagnosis in developed countries, the condition remains underdiagnosed in developing nations such as the Republic of Moldova, where access to genetic testing and family planning services is limited. Routine prenatal screening usually includes regular ultrasounds, monitoring of blood pressure, complete blood counts, coagulation studies, glucose, urine protein, and urine culture. Current ultrasound techniques have limitations in detecting this syndrome due to variability in interpretation, and genetic testing is often performed based on clinical discretion. The ultrasound could potentially point towards a genetic problem, as in DiGeorge, if multiple cardiac malformations are spotted in utero, but most cases such as this one are diagnosed after birth while being described as totally normal on prenatal ultrasound. Purpose: This study aims to highlight the diagnostic challenges and the need for comprehensive evaluation in identifying DiGeorge syndrome, emphasizing the importance of considering the syndrome as a whole rather than focusing on isolated organ system issues. Method: We present a case report of a 6-month-old girl who, after an uneventful pregnancy and normal prenatal ultrasound, presented with cardiac insufficiency. Following extensive investigations and multiple surgical interventions, DiGeorge syndrome was diagnosed at 9 months of age. Results: The patient’s diagnosis was delayed due to the lack of prenatal markers and the reliance on separate investigations of affected organ systems. Despite several interventions aimed at managing her symptoms, the final diagnosis was made after observing the association of multiple clinical features and conducting comprehensive genetic testing. Conclusions: This case underscores the importance of a holistic approach to diagnosis, which involves a thorough patient history, integration of diverse diagnostic tests, and recognition of the syndrome’s multi-system nature. It highlights the necessity for improved diagnostic protocols and increased awareness in regions with limited access to advanced genetic testing to prevent delays in identifying DiGeorge syndrome and to facilitate timely and appropriate management.

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).

Prenatal diagnosis of congenital fetal heart abnormalities and clinical analysis

Objective: To study the value of detecting fetal congenital heart disease (CHD) using the five transverse planes technique of fetal echocardiography. Methods: Nine hundred and eighty-two high-risk pregnancies for fetal CHD were included in this study, the fetal heart was scanned with the five transverse planes technique of fetal echocardiography described by Yagel, autopsy was conducted when pregnancy was terminated. Blood from fetal heart was collected for fetal chromosome analysis. A close follow-up was given for normal fetal heart pregnancies and neonatal echocardiography was performed to check the accuracy of prenatal diagnosis. Results: (1) Forty-six cases (4.68%) were found to have fetal heart abnormalities in this study, 69.56% of them were diagnosed by single four-chamber view, another 30.43% fetal CHD were found by combining other views; (2) Forty-one parents of prenatal fetuses with CHD chose to terminate pregnancy, thirty-two of them gave consent to conduct autopsy, 93.75% of which yielded unanimous conclusion between prenatal fetal echocardiography and autopsy; (3) Thirty-two of 46 cases underwent fetal chromosome analysis, 8 cases (25%) were found to have abnormal chromosome; (4) Five cases were found to have right ventricle and atrium a little bigger than those on the left side, with the unequal condition being the same after birth, but there were no clinical manifestations and they are healthy for the time being; (5) Nine hundred and thirty-six cases were not found with abnormality in this study, but one case was diagnosed with ventricular septal defect after birth, one case was diagnosed with patent ductus arteriosus, one case had atrial septal defect after birth. Conclusions: (1) The detected CHD rate was 4.68% by screening fetal heart with five transverse planes according to Yagel’s description of high risk population basis for CHD. The coinciding rate of prenatal diagnosis and autopsy was 93.75%; (2) The sensitivity of detecting fetal heart abnormality is 92%, the specificity is 99.6% using the five transverse planes technique of fetal echocardiography; (3) Fetuses with mild or moderate disproportion of right and left side in the heart are potentially healthy babies.

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）

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.

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.

A unified model for diagnosing energy usage abnormalities in regional integrated energy service systems

An integrated energy service company in an industrial park or commercial building is responsible for managing all energy sources in their local region, including electricity, water, gas, heating, and cooling. To reduce energy wastage and increase energy utilization, it is necessary to perform efficiency analyses and diagnoses on integrated energy systems(IESs). However, the integrated energy data necessary for energy efficiency analyses and diagnoses come from a wide variety of instruments, each of which uses different transmission protocols and data formats. This makes it challenging to handle energy-flow data in a unified manner. Thus, we have constructed a unified model for diagnosing energy usage abnormalities in IESs. Using this model, the data are divided into working days and non-working days, and benchmark values are calculated after the data have been weighted to enable unified analysis of several types of energy data. The energy-flow data may then be observed, managed, and compared in all aspects to monitor sudden changes in energy usage and energy wastage. The abnormal data identified and selected by the unified model are then subjected to big-data analysis using technical management tools, enabling the detection of user problems such as abnormalities pertaining to acquisition device, metering, and energy usage. This model facilitates accurate metering of energy data and improves energy efficiency. The study has significant implications in terms of fulfilling the energy saving.

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.

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]

Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

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.

Clinical study in diagnosis of placental implantation abnormality with transabdominal Doppler ultrasound

Objective: To evaluate the ultrasonographic charateristics and the diagnostic value in placental implantation abnormality (PIA) with transabdominal Doppler ultrasound, and improve the rate of diagnosis accuracy in the prenatal and postnatal of PIA with transabdominal Doppler ultrasound, for early diagnosis and treatment, to avoid hysterectomy caused by fatal bleeding. Methods: There were 61 cases complicated with PIA by operation and pathologically confirmed in our hospital. 33 cases were prenatal PIA, and 28 cases were postnatal PIA. The sonographic characteristics of PIA were summarized, the sensitivity and false negative rate of transabdominal Doppler ultrasound were analyzed with the results of surgical and pathological diagnosis. Results: In the images of prenatal PIA, the incidence of abundant blood flow signals in muscular layer of the placenta was the highest, which could reached 85.7%, followed by placenta 'vortex' and placenta previa;placental remnants were major sonographic performance in postnatal PIA, the incidence rate was 100%, followed by abundant blood flow signals in muscular layer of the placenta and disappeared boundary between myometrium and placenta. 14 cases could be diagnosed as prenatal PIA accurately by transabdominal Doppler ultrasound, the sensitivity was 42.4%, and the false negative rate was 57.6%. 21 cases could be diagnosed as postnatal PIA accurately by transabdominal Doppler ultrasound, the sensitivity was 75.0%, and the false negative rate was 25.0%. Conclusions: The specificity was low in prenatal PIA by transabdominal Doppler ultrasound, but the false negative rate was high. If necessary, the diagnostic accuracy could be improved combined with MRI. The specificity was much higher in postnatal PIA, and the false negative rate was low. The ultrasonography of PIA has some certain characteristics, we should strengthen the consciousness of the diagnosis in PIA, especially in the prenatal PIA, and improve the auxiliary diagnosis.

Sonographic markers for early diagnosis of fetal malformations

Fetal malformations are very frequent in industrialized countries.Although advanced maternal age may affect pregnancy outcome adversely,80%-90%of fetal malformations occur in the absence of a specific risk factor for parents.The only effective approach for prenatal screening is currently represented by an ultrasound scan.However,ultrasound methods present two important limitations:the substantial absence of quantitative parameters and the dependence on the sonographer experience.In recent years,together with the improvement in transducer technology,quantitative and objective sonographic markers highly predictive of fetal malformations have been developed.These markers can be detected at early gestation(11-14 wk)and generally are not pathological in themselves but have an increased incidence in abnormal fetuses.Thus,prenatal ultrasonography during the second trimester of gestation provides a"genetic sonogram",including,for instance,nuchal translucency,short humeral length,echogenic bowel,echogenic intracardiac focus and choroid plexus cyst,that is used to identify morphological features of fetal Down’s syndrome with a potential sensitivity of more than 90%.Other specific and sensitive markers can be seen in the case of cardiac defects and skeletal anomalies.In the future,sonographic markers could limit even more the use of invasive and dangerous techniques of prenatal diagnosis(amniocentesis,etc.).

Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs:A literature review

Chronic myeloid leukemia(CML)is a myeloproliferative neoplasm and was the first neoplastic disease associated with a well-defined genotypic anomaly―the presence of the Philadelphia chromosome.The advances in cytogenetic and molecular assays are of great importance to the diagnosis,prognosis,treatment,and monitoring of CML.The discovery of the breakpoint cluster region(BCR)-Abelson murine leukemia(ABL)1 fusion oncogene has revolutionized the treatment of CML patients by allowing the development of targeted drugs that inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein.Tyrosine kinase inhibitors(known as TKIs)are the standard therapy for CML and greatly increase the survival rates,despite adverse effects and the odds of residual disease after discontinuation of treatment.As therapeutic alternatives,the subsequent TKIs lead to faster and deeper molecular remissions;however,with the emergence of resistance to these drugs,immunotherapy appears as an alternative,which may have a cure potential in these patients.Against this background,this article aims at providing an overview on CML clinical management and a summary on the main targeted drugs available in that context.