Utility of fetal facial markers on a second trimester genetic sonogram in screening for Down syndrome in a high-risk Thai population

Background To establish the reference ranges and evaluate the efficacy of the fetal facial sonomarkers prenasal thickness (PT), nasal bone length (NBL), PT/NBL ratio and NBL/PT ratio for Down syndrome screening in the second trimester of high-risk pregnancies using two-dimensional (2D) ultrasound. Methods A prospective study was done in Thai pregnant women at high risk for structural and chromosomal abnormalities between May 2018 and May 2019. The main exclusion criteria were any fetal anatomical anomaly detected on ultrasonography or postpartum examination, abnormal chromosome or syndrome other than Down syndrome. Ultrasounds were performed in 375 pregnant women at 14 to 22 weeks’ gestation and the fetal facial parameters were analyzed. Down syndrome results were confirmed by karyotyping. The reference ranges of these facial ultrasound markers were constructed based on the data of our population. The Down syndrome screening performance using these facial ultrasound markers was evaluated. Results In total, 340 euploid fetuses and 11 fetuses with Down syndrome met the inclusion criteria. The PT, NBL, and PT/NBL ratios in the euploid fetuses gradually increased with gestation progression while the NBL/PT ratio gradually decreased between 14–22 weeks’ gestation. The NBL, PT/NBL ratio, and NBL/PT ratio all had 100% sensitivity and PT had 91% sensitivity. These facial markers had 100% negative predictive value for Down syndrome screening in the second trimester. The Bland–Altman analysis showed the intra- and inter-observer variations of PT and NBL had high intraclass correlation coefficients (ICC) in both operators, with ICCs of 0.98 and 0.99 and inter-observer ICCs of 0.99 for both operators. Conclusion The facial ultrasound markers are very useful for second trimester Down syndrome screening in our population. These facial ultrasound markers were easily identifiable and highly consistent either intra- or inter-operator by using widely-available 2D ultrasound. However, the reference ranges for these markers need to be constructed based on individual populations. Trial registration Registration number: REC 61–029-12–3. Date of registration: 18 May 2018.

The Prognostic Impact of MYC Gene-Related Abnormalities on Multiple Myeloma Outcome through Fluorescence in situ Hybridization Analysis

Introduction: Chromosomal abnormalities (CAs) have been identified as important factors in determining the biological features and prognostic value of multiple myeloma (MM). MYC gene-related abnormalities (MYC GAs) are one of the CAs, but its unfavorable impact has not been fully investigated in daily clinical practice. Methods: This study retrospectively analyzed the prognostic impact of MYC GAs on 81 patients through fluorescence in situ hybridization analysis in our institute. Results: MYC GAs were associated with poor overall survival (hazard ratio [HR], 3.08; 95% confidence interval [CI], 1.23–7.73; p = 0.017), progression-free survival (PFS) (HR, 2.96; 95% CI, 1.58–5.53; p < 0.001), and time to next treatment (TNT) (HR, 2.11; 95% CI, 1.13–3.93; p = 0.018) in the median follow-up of 34.7 months. Furthermore, MYC GAs with an additional chromosome 8 (MYC-Ch8(+)) were associated with shorter PFS (HR, 3.15; 95% CI, 1.38–7.2; p = 0.0064), whereas MYC GAs without an additional chromosome 8 (MYC-Ch8(−)) were associated with shorter PFS (HR, 3.62; 95% CI, 1.51–8.68; p = 0.004) and shorter TNT (HR, 3.72; 95% CI, 1.41–9.81; p = 0.0078). Conclusion: These findings could help identify high-risk patients with MM. Further prospective studies are needed to confirm the significance of MYC GAs for the MM prognostic effect.

Seropositivity for CMV, EBV, HBV, HCV, and HIV in Leukemia Patients and Its Relationship with Cytogenetic Changes

Introduction: Leukemias are involving the bone marrow and the soft tissues in inner parts of the bones, where new blood cells are formed. This malignancy is the most common pediatric cancer, which its etiologic causes are not well understood. This multifactorial disease is believed to linked with genetic and non-hereditary environmental factors. Cytogenic analyses of chromosomal abnormalities provide diagnostic and prognostic values in leukemia patients. Given the high prevalence of viral diseases and clinical suspicions on the relationship between certain viral infections and leukemia, it is necessary to investigate this possible relationship, especially in third-world countries. The present study recruited 65 children with leukemia (AML, CML, or ALL) who were presented to two tertiary hospitals. At first, all the patients underwent testing for HBV, HCV, CMV, EBV, and HIV. Bone marrow specimens were studied for identifying possible chromosomal abnormalities in cytogenic investigations. According to our findings, there was a relationship between incidence of leukemia, the 12:21 chromosomal translocation and CMV infection. Therefore, preventing CMV infection can lead to a reduced incidence of leukemia. It is expected that the findings of this study enlighten the scientists to conduct more extensive research on the relationship between viral diseases and leukemia in third-world countries.Method:The present study recruited 65 children with leukemia (AML, CML, or ALL) who were presented to two tertiary hospitals. At first, all the patients underwent testing forHBV, HCV, CMV, EBV, and HIV. Bone marrow specimens were studied for identifying possible chromosomal abnormalities in cytogenic investigations.Result:According to our findings,there was a relationship between the incidence of leukemia,the 12:21 chromosomal translocation, and CMV infection.Therefore, preventing CMV infection can lead to a reducedincidence of leukemia.Conclusion:In this study, we demonstrated that leukemia is relevant to the 12:21 chromosomal translocation and CMV virus infections, So the reduction in leukemia prevalence is dependent on the prevention of CMV disease. It is expected that the findings ofthis studyenlighten the scientists to conduct more extensive researchon the relationship between viral diseasesand leukemia in third-world countries.Trial registrations:Clinical trial registration code:IR.AJAUMS.REC.1399.161Evaluated by: AJA UNIVERSITY OF MEDICAL SCIENCESApproval Date:2020-11-15Approval statement: The project was found to be in accordance with the ethical principles and the national norms and standards for conducting Medical Research in Iran.

Genetic Counseling and Management: The First Study to Report NIPT Findings in a Romanian Population

Background and Objectives: Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, 13, sex chromosomes aneuploidies and several microdeletions. This study aimed to assess the accuracy of cell free DNA testing based on low-level whole-genome sequencing to screen for these chromosomal abnormalities and to evaluate the clinical performance of NIPT. Materials and Methods: 380 consecutive cases from a single genetic center, from Western Romania were included in this retrospective study. Cell-free nucleic acid extraction from maternal blood, DNA sequencing and analysis of sequenced regions were performed by BGI Hong Kong and Invitae USA to determine the risk of specific fetal chromosomal abnormalities. In high-risk cases the results were checked by direct analysis of fetal cells obtained by invasive methods: 6 chorionic villus sampling and 10 amniocenteses followed by combinations of QF-PCR, karyotyping and aCGH. Results: NIPT results indicated low risk in 95.76% of cases and high risk in 4.23%. Seven aneuploidies and one microdeletion were confirmed, the other results were found to be a false-positive. A gestational age of up to 22 weeks had no influence on fetal fraction. There were no significant differences in fetal fraction across the high and low risk groups. Conclusions: This is the first study in Romania to report the NIPT results. The confirmation rate was higher for autosomal aneuploidies compared to sex chromosome aneuploidies and microdeletions. All cases at risk for trisomy 21 were confirmed. Only one large fetal microdeletion detected by NIPT has been confirmed. False positive NIPT results, not confirmed by invasive methods, led to the decision to continue the pregnancy. The main limitation of the study is the small number of patients included. NIPT can be used as a screening method for all pregnancies, but in high-risk cases, an invasive confirmation test was performed.

Estimating the frequency of causal genetic variants in foetuses with congenital heart defects: a Chinese cohort study

Background The belief that genetics plays a major role in the pathogenesis of congenital heart defects (CHD) has grown popular among clinicians. Although some studies have focused on the genetic testing of foetuses with CHD in China, the genotype–phenotype relationship has not yet been fully established, and hotspot copy number variations (CNVs) related to CHD in the Chinese population are still unclear. This cohort study aimed to assess the prevalence of chromosomal abnormalities in Chinese foetuses with different types of CHD. Results In a cohort of 200 foetuses, chromosomal abnormalities were detected in 49 (24.5%) after a prenatal chromosome microarray analysis (CMA), including 23 foetuses (11.5%) with aneuploidies and 26 (13.0%) with clinically significant CNVs. The additional diagnostic yield following whole exome sequencing (WES) was 11.5% (6/52). The incidence of total chromosomal abnormality in the non-isolated CHD group (31.8%) was higher than that in the isolated CHD group (20.9%), mainly because the incidence of aneuploidy was significantly increased when CHD was combined with extracardiac structural abnormalities or soft markers. The chromosomal abnormality rate of the complex CHD group was higher than that of the simple CHD group; however, the difference was not statistically significant (31.8% vs. 23.6%, P = 0.398). The most common CNV detected in CHD foetuses was the 22q11.2 deletion, followed by deletions of 5p15.33p15.31, deletions of 15q13.2q13.3, deletions of 11q24.2q25, deletions of 17p13.3p13.2, and duplications of 17q12. Conclusions CMA is the recommended initial examination for cases of CHD in prenatal settings, for both simple heart defects and isolated heart defects. For cases with negative CMA results, the follow-up application of WES will offer a considerable proportion of additional detection of clinical significance.

Prevalence of common aneuploidy in twin pregnancies

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04–0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Stud-breeding work in sheep breeding based on cytogenetic monitoring

The article presents the results of the cytogenetic monitoring in the breeding, selection and reproduction of sheep in the ecological conditions of Ukraine. A cytogenetic analysis of sheep with low and high vigor and different levels of fertility was carried out. In the ecological conditions of Ukraine, the individual level of chromosomal abnormalities in all the studied animals of the Tsigai breed and prekos is within the natural background. No translocations were found. Among the violations, such as single and paired fragments, hypo- and hyperploidy (mainly hypoploidy), polyploidy were encountered. The maximum average level of chromosomal abnormalities was found in local lambs (5.5 ±1.73%). The minimum average level of chromosomal abnormalities (2.0 ±1.41%) was recorded in lambs with high growth intensity. Among the structural changes, mutations of the chromosomal type prevailed in the 3-year-old group of rams - 0.46%, in the 8-year-old group - 0.59%. Chromatid disturbances were 0.37% and 0.34%, respectively. The average level of chromosomal abnormalities in rams by groups was 0.84 ±0.14 and 0.93 ±0.13, respectively. In the group of ewes with low fertility (n = 4), the level of chromosomal abnormalities was 3.5%, which is lower than ewes (n = 7) with high fertility by 0.79%.

Stillbirth and Neonatal mortality in Jordan: Findings from Jordan Stillbirths and Neonatal Deaths Surveillance System (Preprint)

BACKGROUND Stillbirth and neonatal mortality declined significantly in high- and some middle- income countries because of the significant improvements in obstetric and neonatal care. Yet, stillbirth and neonatal mortality rates remain high in low-income countries. The main reason for low progress in reducing such stillbirths and neonatal deaths in Jordan is the scarcity of data on causes and contributing factors leading to these deaths. OBJECTIVE This study aimed to determine the rates, causes and risk factors of stillbirth and neonatal mortality in Jordan. METHODS An electronic stillbirth and neonatal deaths surveillance system was established in five large hospitals in Jordan. Data on all births, stillbirths and neonatal deaths and their causes during the period May 2019 – December 2020 were exported from the system and analyzed. RESULTS A total of 29,592 women gave birth to 31,106 babies during a period of 20 months in the selected hospitals. The stillbirth rate was 10.5 per 1,000 total births, the neonatal death rate was 14.2 per 1,000 live births, and the perinatal death rate was 21.4 per 1,000 total births. Of all neonatal deaths, 29.4% died within the first day of life and 77.8% died during the first week of life. For neonatal deaths occurred pre-discharge, the leading causes of death were respiratory and cardiovascular disorders (35.0%), low birth weight and prematurity (32.7%), and congenital malformations, deformations and chromosomal abnormalities (19.5%). Almost one third of stillbirths had unspecified cause of death (33.3% of antepartum stillbirths and 28.9% of intrapartum stillbirths). Acute antepartum event was responsible of 27.4% of antepartum stillbirths and acute intrapartum event was responsible for 13.2% of intrapartum stillbirths. Congenital malformations, deformations and chromosomal abnormalities contributed to 18.1% of antepartum stillbirths and 34.2% of intrapartum stillbirths. CONCLUSIONS There is a relative stability of stillbirth and neonatal mortality rates in Jordan. Several identified maternal and/or fetal conditions that contributed to stillbirths and/or neonatal deaths in Jordan are preventable. Focused care needs to be directed high-risk pregnant women and to neonates with low birthweight and respiratory problems.

Сytogenetic techniques in current biomedical research. part i: history and theoretical basis of human cytogenetics

Cytogenetics is an essential part of human genetics which studies the structure of chromosomes and their collection which is called karyotype. Cytogenetic techniques are employed while interrogating DNA organisation and compaction. Analysis of the chromosomal structure contributes to uncovering the molecular basis of various cellular processes in normal and pathological conditions. Furthermore, spectrum and frequency of chromosome abnormalities serves as an indicator of mutagenic effects. Cytogenetic techniques became indispensable for discovering the genetic causes of human diseases at different stages of ontogenesis. Genetic abnormalities are a common cause of impaired reproductive function, abnormal pregnancy, and neonatal malformations. Genetic screening for chromosomal abnormalities and congenital anomalies is a powerful tool for reducing the genetic load in human populations as well as disease, psychological and social burden on families and societies. This paper begins the cycle of lectures on molecular basis of human cytogenetics, cytogenetic techniques, and the corresponding research and clinical applications. The lecture is primarily aimed at biomedical students and physicians who often have an unmet need to analyse and interpret the results of cytogenetic analyses.