Prevalence Of Chromosomal Abnormalities Research Articles

The prevalence of congenital anomalies: nationwide study in 2020 in Estonia

Objective To assess the prevalence of congenital anomalies (CAs), chromosomal abnormalities and monogenic diseases among births and terminated pregnancies due to fetal anomalies (TOPFA) in 2020 in Estonia. Up to 2020 no data on prevalence of CAs in Estonia is reported. Methods For retrospective observational study data of all births and terminations of pregnancies after 12th gestational week from (i) the Estonian Medical Birth Registry, (ii) Abortion Registy, (iii) Health Insurance Fund and (iv) hospital records were linked. To calculate the total, live birth, stillbirth and TOPFA prevalence of CAs with 95% confidence intervals (CI), guidelines issued by EUROCAT, European network for the epidemiological surveillance of CAs, https://eu-rd-platform.jrc.ec.europa.eu/eurocat_en were followed. Results In 2020 the total prevalence of CAs, chromosomal abnormalities and monogenic diseases in Estonia was 378.6 per 10,000 births (95% CI 346.0, 413.5). The most prevalent CAs were heart defects, 163.7 cases per 10,000 births (95%CI 142.5, 187.2). The prevalence of chromosomal abnormalities and genetic diseases was 92.6 per 10,000 births (95%CI 76.8, 110.6), 80% of cases were among TOPFAs. No newborns with major aneuploidies (Trisomy 21, 18, 13, polyploidy) were reported in 2020. Live birth prevalence of CAs, including chromosomal abnormalities and genetic diseases was 258.4 per 10,000 live births (95%CI 231.5, 287.5) and stillbirth prevalence of CAs 0.8 per 10,000 births. Conclusions The prevalence of CAs and genetic disorders in Estonia is one of the highest compared to prevalence reported by other European regions. It indicates to high population coverage with prenatal diagnostics in Estonia. Low number of major aneuploidies among live births may reflect good detection rate of major chromosomal abnormalities and cultural preferences.

Green synthesis and characterization of aluminum oxide nanoparticles using Phoenix dactylifera seed extract along with antimicrobial activity, phytotoxicity, and cytological effects on Vicia faba seeds

AbstractThe present study assessed the green synthesis of aluminum oxide nanoparticles (Al2O3-NPs) by using aluminum (Al) foil waste as an Al source and date palm seed extract as a reducing and stabilizing agent. Several methodologies were employed to investigate Al2O3-NPs, encompassing X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray (EDX) analysis. The UV–visible spectroscopy analysis revealed the presence of an absorption peak at a wavelength of 264 nm, providing evidence for the successful green synthesis of the Al2O3-NPs. The XRD analysis revealed that the average size of the Al2O3-NPs was 32 ± 2.57 nm and had a rhombohedral structure. The EDX facilitated the identification of the elemental composition of the sample, which was found to consist of 40.37% Al and 31.56% O, confirming the high purity of the Al2O3-NPs powder. Furthermore, it was noted that the Al2O3-NPs exhibited the greatest antibacterial efficacy against Candida albicans (21 ± 1.85 mm), but no discernible antimicrobial effect was recorded against Klebsiella pneumoniae at higher concentrations of Al2O3-NPs. No significant variation in the germination of faba bean seeds was observed upon treatment with Al2O3-NPs. The observed mitotic index in the treatment group was determined to be significantly lower compared to the control cells, based on the duration and dosage of Al2O3-NP exposure. In contrast, for micronuclei (MN) and the prevalence of chromosomal abnormalities, there is a noticeable upward trajectory in this phenomenon. Finally, Al2O3-NPs are employed in a variety of applications, such as biomedical and agriculture.

Single nucleotide polymorphism array (SNP-array) analysis for fetuses with abnormal nasal bone.

This study aims to evaluate the prevalence of submicroscopic chromosomal abnormalities found on single nucleotide polymorphism array (SNP array) in pregnancies with either an absent or hypoplastic nasal bone. This retrospective study included 333 fetuses with either nasal bone hypoplasia or absence identified on prenatal ultrasound. SNP array analysis and conventional karyotyping were performed in all the subjects. The prevalence of chromosomal abnormalities was adjusted for maternal age and other ultrasound findings. Fetuses with either an isolated nasal bone absence or hypoplasia, those that had additional soft ultrasound markers, and those where structural defects were found on ultrasound were divided into three groups: A, B, and C, respectively. Among the total cohort of 333 fetuses, 76 (22.8%) had chromosomal abnormalities, including 47 cases of trisomy 21, 4 cases of trisomy 18, 5 cases of sex chromosome aneuploidy, and 20 cases of copy number variations of which 12 were pathogenic or likely pathogenic. The prevalence of chromosomal abnormalities in group A (n = 164), B (n = 79), and C (n = 90) was 8.5%, 29.1% and 43.3%, respectively. The incremental yields by SNP-array compared with karyotyping in group A, B, and C were 3.0%, 2.5% and 10.7%, respectively (p > 0.05). Compared to karyotype analysis, SNP array detected an additional 2 (1.2%), 1 (1.3%), and 5 (5.6%) pathogenic or likely pathogenic CNVs in groups A, B, and C, respectively. In the 333 fetuses, the prevalence of chromosomal abnormalities in women with advanced maternal age (AMA) was significantly higher than that in non-AMA women, (47.8% vs. 16.5%, p < 0.05). In addition to Down's syndrome, many other chromosomal abnormalities are present in fetuses with abnormal nasal bone. SNP array can improve the prevalence of chromosomal abnormalities associated with nasal bone abnormalities, especially in pregnancies with non-isolated nasal bone abnormalities and advanced maternal age.

Prevalence of Chromosomal Abnormalities in Iranian Patients with Infertility.

The numerical and structural abnormalities of chromosomes are the most common cause of infertility. Here, we evaluated the prevalence and types of chromosomal abnormalities in Iranian infertile patients. We enrolled 1750 couples of reproductive age with infertility, who referred to infertility clinics in Tehran during 2014- 2019, in order to perform chromosomal analysis. Peripheral blood samples were obtained from all couples and chromosomal abnormalities were evaluated by G-banded metaphase karyotyping. In some cases, the detected abnormalities were confirmed using fluorescence in-situ hybridization (FISH). We detected various chromosomal abnormalities in 114/3500 (3.257%) patients with infertility. The prevalence of chromosomal abnormalities was 44/114 (38.596%) among infertile females and 70/114 (61.403%) among infertile males. Structural chromosomal abnormalities were found in 27/1750 infertile females and 35/1750 infertile males. Numerical chromosomal abnormalities were found in 17/1750 of females and 35/1750 of males. The 45, XY, rob (13;14) (p10q10) translocation and Klinefelter syndrome (47, XXY) were the most common structural and numerical chromosomal abnormalities in the Iranian infertile patients, respectively. In general, we found a high prevalence of chromosomal abnormalities in Iranian patients with reproductive problems. Our study highlights the importance of cytogenetic studies in infertile patients before starting infertility treatments approaches.

Hormonal, clinical, and genetic profile of infertile patients with azoospermia in Morocco.

azoospermia affects more than 10%-15% of infertile male subjects attending the infertility center. In Morocco, there have been no studies on male infertility with azoospermia. Thereby, our objective was to evaluate the clinical, hormonal, and genetic characteristics of infertile men with azoospermia in Morocco. we conducted a retrospective descriptive study performed with a convenience sample of 80 infertile men from 2021 to 2022, in the Assisted Reproductive Technology Unit of the Mohammed VI University Hospital Center in Oujda-Morocco. All patients with azoospermia were subjected to a quantitative hormone assay to evaluate the functionality of the sertolic and leydigial compartments. Human karyotyping and AZF microdeletion analysis are routinely performed in azoospermic patients. the results show that the mean age of patients in the study was 45.7 ± 3.5 years. Primary infertility accounts for the majority, with a rate of 96% (n=77). There were 12 cases of azoospermia of secretory origin, 22 cases of excretory origin, and 3 of undetermined origin. Azoospermia was associated with hydrocele in 29% (n=27) of cases. The average levels of FSH, LH, testosterone, and inhibin B were 15.54 ± 5.5 mIU/mL, 7.71 ± 2.7 mIU/mL, 405.09 ± 6.13 ng/dl and 38.44 ± 5.13 pg/ml, respectively. The prevalence of chromosomal abnormalities was 30.7%. Of these, the sex chromosome aneuploidy with 47, XXY karyotype (Klinefelter syndrome) accounted for 11% (n=9). The incidence of microdeletions of azoospermia factors (AZF) was 9%, and AZFc deletion was the most common at the rate of 3%. our research shows that hydrocele, varicocele, and chromosomal abnormalities are the leading causes of azoospermia. In the Moroccan population, azoospermia is essentially of excretory origin.

Ефекти інбридингу на поширеність хромосомних порушень серед населення Слобожанщини

An increase in inbreeding level and advanced parental age are factors that increase the risk of having children with structural and numerical chromosomal abnormalities due to altered frequency of recombination and impaired behavior of chromosomes in meiosis. There is limited information on the effects of inbreeding on human chromosomal and genomic mutations. The purpose of the study was to assess the effect of inbreeding on the prevalence of chromosomal abnormalities in the districts of the Kharkiv region. Materials and methods. The study was conducted in four districts of the Kharkiv region – Balakliia, Vovchansk, Zmiiv, and Krasnograd (administrative and territorial structure is given as of July 1, 2020). Based on the data of analysis of 1,582 marriages between opposite-sex couples mean age at marriage, marital distance, and the random inbreeding coefficient (FST) were estimated. Of 654 children (aged 0–17 years) included in the study, 39 had chromosomal disorders that was the basis for the calculation of the prevalence of chromosomal abnormalities. Results and discussion. In four districts, the mean age at marriage for local residents was 27.8 ± 0.1 years. Men were 2.9 years older than women at marriage. The marital distance was 320.4 ± 28.4 km, varying from 263.17 ± 48.39 km in the Balakliia district to 400.12 ± 79.97 km in the Vovchansk district. The random inbreeding coefficient FST was 0.001292. In rural settlements, the random inbreeding coefficient FST was by 17.2 times higher than in urban settlements. The index rose by 80 percent over the last seven years. The prevalence of chromosomal pathology among children and adolescents was 0.08%, ranging from 0.05% in the Vovchansk district to 0.14% in the Krasnograd district. Among the cases included, there were patients with Down syndrome, Klinefelter syndrome, Turner syndrome, and Prader-Willi syndrome. The most common nosological entity was Down syndrome. The prevalence of chromosomal abnormalities in villages was by 2.6 times higher than in towns. A strong positive relationship was established between the random inbreeding coefficients FST and the prevalence of chromosomal disorders in the study area (r = 0.904). Conclusion. Almost two-fold increase in the inbreeding rate in the mentioned districts in just past seven years may contribute to accumulation of burden of chromosomal disorders of the population due to the presence of a positive correlation between the study population indicators

Prevalence and patterns of chromosomal abnormalities among Egyptian patients with infertility: a single institution\u2019s 5-year experience

BackgroundChromosomal abnormalities represent an important cause of human infertility. Little is known about the prevalence of chromosomal abnormalities among Egyptian couples with infertility. We estimated the cytogenetic profiles and semen analysis patterns among infertile couples. We analyzed data from medical archives of 2150 patients with infertility in Mansoura University Children’s Hospital, Egypt from 2015 to 2019. The data included karyotypes and semen analysis reports.ResultsChromosomal abnormalities were reported in 13.5% of infertile patients (290/2150); 150 out of 1290 (11.62%) males and 140 out of 860 (16.28%) females. Within the infertile males, the numerical chromosomal abnormalities were detected in 134/1290 (10.38%) males, and structural abnormalities were found in 16/1290 (1.24%) males. Within the infertile females, numerical sex chromosome abnormalities were detected in 75/860 (8.72%) females, structural sex chromosome abnormalities were found in 31/860 (3.6%) females, mosaicism of the sex chromosome was found in 22/860 (2.56%) females, and male pseudohermaphrodites were detected in 12/860 (1.39%) females.ConclusionsNumerical chromosomal aberrations are the most frequent patterns among infertile couples. Attention should be paid to the traditional chromosomal analysis as an important diagnostic step in the infertility work-up.

Chromosomal abnormalities and clinical conditions associated with the male infertility among Emirati: 10-year retrospective research study

Background: Male infertility is a global health issue that is poorly described in United Arab Emirates. Methods: In this 10-year retrospective cross-sectional study, we retrieved data of 312 male patients attending Dubai Fertility Center in United Arab Emirates between January 2011 and January 2021. We identified the type and prevalence of chromosomal abnormalities and hormonal and semen abnormalities among Emirati infertile males as compared with regional and global populations. Results: Total chromosomal abnormalities accounted for 13.9% and 8% among azoospermic Emiratis and total Emirati infertile males, respectively. Numerical chromosomal abnormalities causing male infertility were Klinefelter syndrome, 47,XXY (4.0%); Jacob syndrome, 47,XYY (0.8%); mosaic, 48,XXXY/47,XXY/46,XY (0.4%); and mosaic 47,XXY/46,XY (0.4%). Structural chromosomal abnormalities causing male infertility were Y chromosome microdeletion (1.2%), 46,XX/46,XY (0.4%), 46,XY,inv(5)(p15.1q11.2) (0.4%), and 45,XY,der(13;15)(q10;q10) (0.4%). About 59.0% of the Emirati cohort had azoospermia, whereas 28.46% were diagnosed with other conditions of spermatogenic failure as severe oligoasthenoteratozoospermia (7.63%), severe oligoasthenospermia (5.22%), severe oligozoospermia (4.41%), oligoasthenoteratozoospermia (3.6%), asthenozoospermia (2.4%), oligoasthenospermia (1.6%), oligozoospermia (2%), teratozoospermia (0.8%), asthenoteratozoospermia (0.4%), and aspermia (0.4%). As for male hormonal profile of the Emiratis, azoospermic males with chromosomal defects had higher testosterone abnormality (72.2% vs. 45.4%), interstitial-cell stimulating hormone abnormality (66.6% vs. 42.6%), follicle-stimulating hormone abnormality (72.2% vs. 41.5%), and inhibin B hormone abnormality (100% vs. 83.8%) as compared to azoospermic males without chromosomal abnormalities. Conclusion: This is the first study to report conclusively the profiling of chromosomal abnormality among Emirati infertile males, which falls within the regional and global range, and to highlight the critical role of genetic testing and counseling for evaluating male infertility.

Prevalence of cytogenetic abnormalities and FMR1 gene premutation in a Portuguese population with premature ovarian insufficiency.

Chromosome abnormalities contribute to about 10% of cases of premature ovarian insufficiency. Most are associated with X chromosome. Fragile mental retardation 1 (FMR1) gene premutation has an estimated prevalence of 1% - 7% in sporadic cases and up to 13% in familial cases. Our aim was to describe the clinical characteristics, cytogenetic and FMR1 testing of a Portuguese population with premature ovarian insufficiency. Women diagnosed with premature ovarian insufficiency in a Portuguese tertiary centre were retrospectivelyanalysed. Data were retrieved from electronic medical records including clinical characteristics, cytogenetic and FMR1 testing. The main outcome measures were the prevalence of chromosome abnormalities and FMR1 premutation in a Portuguese population withpremature ovarian insufficiency. Ninety-four patients were included, with a median age at menopause of 36 years. The prevalence of chromosome abnormalities was 16.5% (14/85) and most were X chromosome related (78.6%). The prevalence of FMR1 premutation was 6.7% (6/90). The prevalence of karyotypic abnormalities or FMR1 premutation did not differ significantly between familial and sporadic cases. Neither chromosome abnormalities nor FMR1 premutation influenced age at menopause or follicle stimulating hormone levels at diagnosis in premature ovarian insufficiency patients. This is the first study describing the clinical characteristics and both cytogenetic and FMR1 testing in a Portuguese population with premature ovarian insufficiency. The rate of chromosome abnormalities in our sample was higher than in other populations, while the prevalence of FMR1 premutation was similar to previous reports. Our results underline the importance of genetic screening in premature ovarian insufficiency patients in both etiological study and genetic counselling.

Contingent prenatal screening for frequent aneuploidies with cell-free fetal DNA analysis

ObjectiveTo analyze the results of contingent screening for common aneuploidies at our center from June 2017 to June 2019. Materials and methodsTraditional screening tests were performed using a combination of biochemical markers and ultrasound measurements in the first and second trimesters to assess the risk of trisomies 21 (T21), 18 (T18) and 13 (T13). Cell-free DNA (cf-DNA) testing was offered (Harmony test) to pregnant women at high risk (>1/280 for T21 and > 1/150 for T13 and T18) and a normal early morphology scan. In positive cases, prenatal sampling was strongly recommended to confirm the results by gold standard methods (QF-PCR and karyotyping). Newborns' phenotypes were corroborated after birth in all cases. ResultsIn this prospective study, 8153 pregnant women were enrolled, resulting in 390 at high risk according to traditional screening tests. cfDNA testing was offered to 383 women. Traditional screening tests showed a false negative rate of 9.68% for T21. Traditional test sensitivity for T21 was 90.3%, for a false positive rate of 4.17% and a positive predictive value of 7.6%. The positive and negative predictive value for cfDNA testing was 100%. The approach used avoided invasive procedures in 91.3% of women at high risk. The prevalence of chromosomal abnormalities in the population analyzed was 1 in 164, and 1 in 210 for T21. ConclusionsOur results show that offering cf-DNA testing to women at high risk in traditional tests (including those with risks >1 in 50) significantly reduces false positives and, therefore, the number of invasive tests. Extending the use of cf-DNA testing to intermediate risk categories may be cost effective.

Prevalence of Chromosomal Abnormalities in Patients with Consanguineous Marriages Referred to Sarem Women’s Hospital, Tehran, Iran

Prevalence of Chromosomal Abnormalities in Patients with Consanguineous Marriages Referred to Sarem Women’s Hospital, Tehran, Iran

Abstract 2269: The spindle assembly checkpoint as a therapeutic vulnerability in RIT1-mutant lung adenocarcinoma

Abstract Standard care of lung cancer is moving away from chemotherapy in favor of personalized approaches based on specific mutations in each tumor. Genome-sequencing studies have identified somatic mutations in the small GTPase RIT1 (Ras-like in all tissues) in lung adenocarcinoma patients. Of the identified mutations, M90I is the most recurrent. Thousands of patients per year are diagnosed with RIT1-driven cancer, but treatment options are limited. A targeted therapy for RIT1-driven disease could greatly improve patient outcomes. Little is known about how RIT1 drives cellular transformation. To genetically dissect signaling pathways downstream of RIT1, we performed a genome-wide CRISPR/Cas9 screen in isogenic PC9 lung adenocarcinoma cells in which cell survival is dependent on expression of RIT1M90I. We found that RIT1-mutant cells were highly dependent on components of the Spindle Assembly Checkpoint (SAC), including the Aurora kinases (A and B). The SAC is a surveillance mechanism that ensures proper chromosome segregation during mitosis. We hypothesized that RIT1M90I weakened the SAC and rendered cells vulnerable to loss of mitotic regulators. To explore this, we performed time-lapse imaging in HeLa H2B-GFP cells stably expressing RIT1M90I. In parental cells, the median duration of mitosis was 70.5 min (95% CI = 63 – 82 min), while in RIT1M90I-mutant cells, this was reduced to 48 min (95% CI = 45 – 51 min). Mitotic index was unaffected, suggesting that RIT1M90I does not regulate mitotic entry. This difference in mitotic timing was eliminated by treatment with reversine, an inhibitor that abolishes the SAC, demonstrating that RIT1M90I perturbs mitotic timing at the level of the SAC. If RIT1M90I weakens the SAC, we would expect higher prevalence of chromosomal abnormalities (such as chromosome bridges) in RIT1M90I-mutant cells. Indeed, analysis of fixed-cell populations indicated that RIT1M90I-mutant cells showed higher prevalence of mitotic abnormalities (79% of RIT1M90I-mutant cells compared to 46% of parental cells, 95% CI= 15 – 53). These data support the hypothesis that RIT1M90I weakens the SAC and imply that further SAC perturbation could be lethal. To explore this, we performed a small molecule screen of 160 clinically-relevant inhibitors in PC9-RIT1M90I and PC9-KRASG12V cells. Intriguingly, RIT1M90I-mutant cells were more sensitive than RAS-mutant cells to alisertib and barasertib, inhibitors of Aurora kinase A and B, respectively. Furthermore, alisertib or barasertib treatment abrogated soft agar colony formation in RIT1M90I-mutant cells but not in RAS-mutant cells. Together with our functional genomic analysis, we propose a model whereby expression of RIT1M90I weakens the SAC, thereby accelerating mitosis, increasing the abundance of mitotic abnormalities, and rendering cells vulnerable to genetic knockdown of SAC genes or small molecule inhibition of Aurora kinases A/B. Citation Format: Amanda Riley, Athea Vichas, Naomi T. Nkinsi, Phoebe C. Parrish, Shriya Kamlapurkar, Alice H. Berger. The spindle assembly checkpoint as a therapeutic vulnerability in RIT1-mutant lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2269.

Study on clinical and genetic characteristics of male patients with non-obstructive azoospermia

We examined 501 patients with non - obstructive azoospermia to evaluate clinical, subclinical, and genetic characteristics. The results show that the average age of patients in the study was 29.8 ± 5.5 years. Primary infertility accounts for the majority, with a rate of 90.3%. There was 38.6% of patients had a history of mumps orchitis. The average levels of FSH, LH, testosterone were 31.6 ± 16.5 mIU/mL, 15.5 ± 10 mIU/mL and 12.8 ± 7.13 nmol/L, respectively. The prevalence of chromosomal abnormalities was 30.7%. Of these, the sex chromosome aneuploidy with 47,XXY karyotype (Klinefelter syndrome) accounted for 27.3%. The incidence of AZF microdeletion was 13.8%. Of these, AZFc deletion was the most common at the rate of 42.1%, AZFa deletion, which accounted for 2.6%, were the least prevalent, and the frequency of AZFd deletion was 5.3%. However, there was no solitary AZFb deletion, which combined with other AZF deletions with 34.2%. Our research shows that mumps orchitis and chromosomal abnormalities are the leading causes of azoospermia. Screening for genetic abnormalities plays an important role in infertile patients with non - obstructive azoospermia.

Predictive value of aberrant right subclavian artery for fetal chromosome aneuploidy in women of advanced maternal age

BackgroundIn the entire population, an aberrant right subclavian artery (ARSA) is closely associated with chromosomal abnormalities. ARSA with additional ultrasonic findings would increase risk of chromosomal abnormalities. The risk of fetal chromosomal abnormalities increased exponentially with the maternal age. These risks in the advanced maternal age (AMA) group are uncertain. This study aimed to determine the incidence of ARSA in Chinese AMA and non-AMA women and the frequency of aneuploidy among AMA and non-AMA women with ARSA.MethodsThis retrospective study included 13,690 singleton pregnancies, were divided into AMA and non-AMA groups. Integrated obstetric ultrasonic screening, biochemical screening, noninvasive prenatal screening, and fetal karyotype analysis were analyzed.ResultsThe overall incidence of ARSA was 0.69%, with no difference between age groups. The incidence of chromosomal abnormalities in the AMA group (37 / 2860) was much higher than that of the non-AMA group. The risk of chromosomal abnormalities significantly increased with both ARSA detected and additional ultrasound findings. With combined ARSA and AMA, the likelihood of the incidence of chromosomal abnormalities increased. Chimerism (45X / 46XX) was found with isolated ARSA in AMA pregnancies.ConclusionThere is a high prevalence of chromosomal abnormalities in fetuses of AMA women. ARSA increases the risk of chromosomal abnormalities in both age groups, especially combined with ARSA. When ARSA occurs in AMA women, it confers a high likelihood of chromosomal abnormalities.

Prenatal genetic diagnosis of omphalocele by karyotyping, chromosomal microarray analysis and exome sequencing

Objectives The aim of this study is to share our experience in the prenatal diagnosis of omphalocele by karyotyping, chromosomal microarray analysis (CMA) and whole exome sequencing (WES). Methods In this retrospective study, 81 cases of omphalocele were identified from 2015 to 2020. Associated anomalies and prenatal diagnosis based on karyotyping, CMA and WES were analysed. Results Fifty-eight (71.6%) of the 81 foetuses had other ultrasound anomalies. Giant omphalocele was present in 11 cases (13.6%) and small omphalocele was present in 70 cases (86.4%). Chromosomal abnormalities were found in 24 foetuses (29.6%, 24/81), the most common of which were trisomy 18 (58.8%, 11/24) and trisomy 13 (29.2%, 7/24). Compared to isolated omphalocele, non-isolated omphalocele was accompanied by an increased prevalence of chromosomal abnormalities (4.3% (1/23) vs. 39.7% (23/58), χ 2 = 8.226, p = .004). All chromosomal abnormalities were found in small omphalocele. Aside from aneuploidy, CMA showed one pathogenic copy number variants (CNVs) for a detection rate of 1.2%, one variants of unknown significance (VOUS) and one instance of loss of heterozygosity (LOH). WES was performed on 3 non-isolated cases, and one was found to have pathogenic variants. Conclusions The most common genetic cause of omphalocele is aneuploidy and the prevalence of chromosomal abnormalities is increased with non-isolated and small omphalocele. CMA and WES can be useful for providing further genetic information to assist in prenatal counselling and pregnancy management.

Clinical Features and Survival Outcomes in Diabetic Patients with Newly Diagnosed Multiple Myeloma (NDMM) Enrolled in the Connect® MM Registry

Clinical Features and Survival Outcomes in Diabetic Patients with Newly Diagnosed Multiple Myeloma (NDMM) Enrolled in the Connect® MM Registry

Identification of Chromosomal Abnormalities in Early Pregnancy Loss Using a High-Throughput Ligation-Dependent Probe Amplification–Based Assay

Embryonic chromosomal abnormalities are the major cause of miscarriage. An accurate, rapid, and cheap method of chromosome analysis in miscarriage is warranted in clinical practice. Thus, a high-throughput ligation-dependent probe amplification (HLPA)-based method of detecting aneuploidies and copy number variations in miscarriage was developed. A total of 1060 cases of miscarriage were assessed. Each specimen was subjected to quantitative fluorescence (QF)-PCR/HLPA and chromosomal microarray analysis (CMA) in parallel. All 1060 samples were successfully analyzed using both methods; of these samples, 1.7% (18/1060) were identified as having significant maternal cell contamination. Among the remaining 1042 cases without significant maternal cell contamination, QF-PCR/HLPA reached a diagnostic yield of 59.6% (621/1042), which is comparable to the yield of 60.3% (628/1042) with CMA. Compared with CMA results, the sensitivity and specificity of QF-PCR/HLPA in the identification of total pathogenic chromosomal abnormalities were 98.9% and 100%, respectively. Furthermore, the overall prevalence of chromosomal abnormalities in cases of spontaneous abortion was not significantly different from that in cases of recurrent miscarriage (61.3% versus 58.5%). In summary, QF-PCR/HLPA rapidly and accurately identified chromosomal abnormalities at a comparable performance and lower cost as compared with CMA. Combining simplicity and accuracy with cost-effectiveness, QF-PCR/HLPA may serve as apromising approach to routine genetic testing in miscarriage in clinical practice.

Study of frequency and types of chromosomal abnormalities in phenotypically female patients with amenorrhea in Eastern Indian population.

This comprehensive review article aims to comprehend the frequency and prevalence of chromosomal abnormalities in both primary amenorrhea (PA) and secondary amenorrhea (SA) cases and correlating it with their phenotypes, clinical features and hormonal profiles. Research publications on prevalence of chromosomal abnormalities in both PA and SA cases worldwide and its etiology, clinical features, hormonal profiles; their correlation with chromosomal profiles were searched for on the internet, including general search engines and respective scientific sites. Only published, relevant and authentic data conducted on phenotypically female patients were considered. Another aspect of amenorrhea occurs due to several clinical conditions apart from cytogenetic viewpoint were not considered or discussed in detail. As literature study suggests; considering various etiology of amenorrhea counting anatomic defect of the hypothalamus or genetic defect, and various acquired causes of chromosomal anomalies contribute to be one of the major etiologies of both PA and SA; ranging from 15.9% to 63.3% in case of PA and from 3.9% to 44.4% in case of SA. In spite of the presence of any other factors responsible condition, the genetic factors need to be emphasized, which might include single gene disorders or chromosomal disorders. Individuals with chromosomal anomalies reported a wide range of abnormalities in phenotypes, as well as in other clinical features and hormonal profiles. This comprehensive review is the first structured review article that encompasses the cytogenetic profile of the amenorrhea cases and correlating it with their phenotypes, clinical features and hormonal profiles from Eastern India.

Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis.

BACKGROUNDRecurrent pregnancy loss (RPL) occurs in 1–3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses.OBJECTIVE AND RATIONALEThe aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses.SEARCH METHODSRelevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale.OUTCOMESFrom a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79–1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86–1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55–1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06–4.56).WIDER IMPLICATIONSA difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present.

Chromosomal Aberrations in 224 Couples with Recurrent Pregnancy Loss.

Background:Recurrent pregnancy loss (RPL) is a major reproductive health issue, affecting 2%–5% of couples. Genetic factors, mainly chromosomal abnormalities, are the most common cause of early miscarriage accounting for 50%–60% of first trimester abortion.Aim:To estimate the prevalence and nature of chromosomal anomalies in couples with recurrent miscarriage.Patients and Methods:This study included 224 couples with a history of 2 or more abortions. Both partners were karyotyped as part of the primary investigation. Cytogenetic analysis was carried out using the standard method.Results:A total of 224 couples with a history of two or more recurrent abortions were enrolled in this study. Chromosomal abnormalities were detected in 26 couples (11.6%) and 28 individuals (6.25%). We found a structural chromosome abnormality in 17/28 patients (60.7%); 12 patients had a reciprocal translocation (42.9%) including one patient with an additional inversion of the Y chromosome, 4 (14.3%) had a Robertsonian translocation, and one patient (3.6%) carried a paracentric inversion of chromosome 2. Numerical chromosome aberrations were detected in 5 patients; three patients (10.7%) with sex chromosome abnormalities and two (7.1%) with a marker chromosome. Six patients (21.4%) showed a heteromorphic variant involving chromosome 9.Conclusion:The prevalence of chromosomal abnormalities in couples with RPL is within the range reported worldwide. Cytogenetic analysis should become an integral part of the investigations of couples with at least two pregnancy losses of undetermined etiology.