Chromosomal Aberrations Research Articles

The Use of Genomic Screening for the Detection of Chromosomal Abnormalities in the Domestic Horse: Five New Cases of 65,XXY Syndrome in the Pura Raza Español Breed.

Sex chromosomal abnormalities are a well-established cause of reproductive failure in domestic horses. Because of its difficult diagnosis, the Pura Raza Español breeding program established a routine screening for chromosomal abnormalities in all the horses prior to enrolling in the studbook. This genomic procedure combines an initial assessment based on the results from Short Tandem Repeat (STR) parentage testing followed by a Single-Nucleotide Polymorphism (SNP) based copy number aberration (CNA) confirmative analysis in positive cases. Using this methodology, we identified five new individuals carrying a 65,XXY chromosomal number aberration (CNA) among 27,330 foals enrolled over the past two reproductive seasons. The animals were initially flagged as CNA candidates due to abnormal results in STR testing. Subsequent analysis genotyping using an STR sex-linked dedicated panel and a medium-density SNP array in ECAX and ECAY confirmed the diagnosis as 65,XXY carriers. Four cases (upon sample availability) underwent further analysis using in situ fluorescent hybridization with ECAX and ECAY probes, showing identical results. Phenotypic analysis revealed abnormal gonad development in one of the cases, showing that the remaining four had a normal reproductive morphology. To our knowledge, this represents the largest number of horses exhibiting the equine form of Klinefelter syndrome (65,XXY) reported to date. Our study highlights the importance of genomic screening in the accurate detection of chromosomal abnormalities in horses.

STUDY OF COPPER COMPLEXES [Cu(LCF3)2] AND [Cu(Lcur)2]H2O AS RADIOPROTECTIVE COMPOUNDS

One of the first and direct signs of the impact of ionizing radiation (IR) on a cell is the destabilization of chromosomes. Radiation-induced damage to the karyotype is an important indicator both for biological indication of the severity of radiation injuries and for predicting the development of long-term adverse effects of IR. The search for new, effective radioprotective compounds is a priority task of modern radiobiology. In this area, metal-based compounds with high antioxidant activity are of particular interest. The purpose of this work is to determine the possible radioprotective properties of Cu(II) complexes, [Сu(LCF3)2] and [Cu(Lcur)2]H2O, supported by the anions of the β-diketone ligands 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (HLCF3) and 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione or curcumin (HLcur). In this research work we determined survival, life expectancy and cytogenetic parameters: mitotic index, chromosome aberrations and % of polyploid cells in the bone marrow cells of the femur (count in 1000 cells in each preparation). Group I included intact animals; Group II consisted of animals exposed to the radioisotope technetium; Group III consisted of animals that were intraperitoneally injected with copper complex [Cu(LCF3)2] at a dose of 50 mg/kg in a volume of 2 mL one hour before the administration of the Tc isotope (“irradiation + copper compound [Cu(LCF3)2]); Group IV included animals that received the compound [Cu(Lcur)2]H2O before irradiation. The groups with the injection of [Cu(LCF3)2] complex had the highest survival. In terms of chromosomal aberrations and number of polyploid cells, as indicators, a significant difference was found in those irradiated compared with the “irradiation + [Cu(LCF3)2]” group (both after 15 and after 30 days), which indicates the radioprotective property of the compound. In terms of the mitotic index, a tendency towards normalization was noted after 15 days and a significant difference between Groups 2 and 3 by the end of the study (after 30 days), which also proves the beneficial effect of this compound. Analysis of survival and changes in cytogenetic parameters multiregression analysis using both complexes confirms the greatest efficiency of the [Cu(LCF3)2] complex with respect to [Cu(Lcur)2]H2O, because when using [Cu(Lcur)2]H2O in Group IV and comparing it with “pure irradiation” only a tendency toward normalization of cytogenetic parameters was observed. Multiregression analysis of cytogenetic parameters also confirmed the highest efficiency of the [Cu(LCF3)2] compound in comparison with [Cu(Lcur)2]H2O. The results of the research indicate the need to continue work in the direction of searching for agents that have a therapeutic effect in radiation injuries.

Advances in pathogenesis research and challenges in treatment development for acute myeloid leukemia.

Acute myeloid leukemia (AML) develops when hematopoietic stem cells acquire chromosomal and genetic abnormalities, transforming into leukemia stem cells (LSCs) and further gaining driver mutations. Advances in genomic analysis have identified numerous new gene mutations involved in AML development. Recent research has shown that individuals with germline mutations in genes like DDX41 and CEBPA develop AML upon acquiring additional somatic mutations, and the latest WHO classification separates AML with such mutations into distinct disease groups. LSCs are regulated by different metabolic processes than normal stem cells, contributing to drug resistance and relapse. LSCs rely on oxidative phosphorylation (OXPHOS) metabolism for energy production, and venetoclax inhibits this process, affecting LSCs. Resistant LSCs show enhanced glycolysis, which suggests that targeting both OXPHOS and glycolysis is crucial. While targeted therapies like FLT3, BCL-2, and IDH inhibitors have shown efficacy, resistance remains an issue, highlighting the need for new treatment strategies. CAR-T cell therapy is an emerging immunotherapy that shows particular promise for targeting CD123 and CLL-1, with acceptable toxicity. Future developments in CAR-T cell therapy and other immunotherapies are anticipated to improve AML treatment outcomes.

Positive Selection Drives the Evolution of the Structural Maintenance of Chromosomes (SMC) Complexes.

Structural Maintenance of Chromosomes (SMC) complexes are an evolutionary conserved protein family. In most eukaryotes, three SMC complexes have been characterized, as follows: cohesin, condensin, and SMC5/6 complexes. These complexes are involved in a plethora of functions, and defects in SMC genes can lead to an increased risk of chromosomal abnormalities, infertility, and cancer. To investigate the evolution of SMC complex genes in mammals, we analyzed their selective patterns in an extended phylogeny. Signals of positive selection were identified for condensin NCAPG, for two SMC5/6 complex genes (SMC5 and NSMCE4A), and for all cohesin genes with almost exclusive meiotic expression (RAD21L1, REC8, SMC1B, and STAG3). For the latter, evolutionary rates correlate with expression during female meiosis, and most positively selected sites fall in intrinsically disordered regions (IDRs). Our results support growing evidence that IDRs are fast evolving, and that they most likely contribute to adaptation through modulation of phase separation. We suggest that the natural selection signals identified in SMC complexes may be the result of different selective pressures: a host-pathogen arms race in the condensin and SMC5/6 complexes, and an intragenomic conflict for meiotic cohesin genes that is similar to that described for centromeres and telomeres.

Evaluation of Cyto-Genotoxic Effects of Mucuna Bracteata DC. Ex Kurz Leaf Extracts by Allium Cepa

This study was conducted to evaluate the cyto-genotoxicity of leaf decoctions of Mucuna bracteata by Allium cepa bioassay. This kind of study can be used as a baseline monitoring system for plant products before their use. It is an inexpensive, simple, and reliable test to determine the cytotoxic and genotoxic effects of various plant extracts on living organisms. In this experiment, Allium cepa bulbs were placed in five concentrations (0.5 mg/mL, 2.5 mg/mL, 5.0 mg/mL, 7.5 mg/mL, and 10.0 mg/mL) of leaf decoction, with tap water as the negative control and 20.0 µL/L EMS (Ethylmethene sulphonate) as the positive control. Each concentration had five replicates. The cyto-genotoxicity assay exhibited a dose-dependent influence on the mitotic index. The mitotic index of the negative control and the positive control were 16.8 ± 0.37% and 6.86 ± 1.71%, respectively. The lowest dose of the extract, 0.5 mg/mL, had the highest mitotic index (14.2 ± 0.73%), while the highest dose, 10.0 mg/mL, had the lowest (9.6 ± 0.40%), and all indices were significantly higher than the positive control. Except for the 10 mg/mL concentration, the mitotic indices of other concentrations were significantly lower than the negative control. Different types of chromosome disorders, namely, disorderly prophase, sticky chromosomes, chromosome bridges, laggard chromosomes, pole deviation, vagrant chromosomes, nuclear filaments with terminal expansion, c-mitosis, micronuclei, and elongated nuclei, were observed. Various changes in root size, growth, and color were revealed by macroscopic examinations. Tumors were formed in roots at the highest doses but not at lower concentrations. Therefore, M. bracteata leaf extract showed cytotoxic and genotoxic effects on the Allium root meristem. J. Bio-Sci. 32(2): 71-82, 2024

Comparison of disease and risk classifications of AML before and after incorporation of NGS analysis of bone marrow samples.

Mutation profiling by next-generation sequencing (NGS) has facilitated understanding of the molecular pathogenesis of acute myeloid leukemia (AML), and has been incorporated into the new disease classification (International Consensus Classification; ICC) and risk classification (European LeukemiaNet [ELN] 2022; ELN2022). We compared disease subtypes between the previous disease classification (4th edition of the WHO classification; WHO-4) and the ICC in 91 patients with AML diagnosed at our institution. We also compared disease risk classifications using the previous risk classification (ELN2017) and the ELN2022. Targeted sequencing of bone marrow samples was conducted at Kyoto University. We found that entities under AML with recurrent genetic abnormalities were well-established, with almost no change from the WHO-4 to the ICC. In contrast, 16.7% of cases of AML, not otherwise specified in the WHO-4 were reclassified into AML with mutated TP53, and 36.7% were reclassified into AML with myelodysplasia-related gene mutations or cytogenetic abnormalities per the ICC. Meanwhile, the ELN2017 and ELN2022 showed no difference in concordance indexes in multivariate Cox regression analysis for progression-free and overall survival. The superiority of the ELN2022 over the ELN2017 could not be confirmed in our single-center retrospective study, and further investigation including multicenter prospective studies is needed.

Generation and analysis of mouse embryonic stem cells with knockout of the Mcph1 (microcephalin) gene.

Chromatin is not randomly distributed within the nucleus, but organized in a three-dimensional structure that plays a critical role in genome functions. Сohesin and condensins are conserved multi-subunit protein complexes that participate in mammalian genome organization by extruding chromatin loops. The fine temporal regulation of these complexes is facilitated by a number of other proteins, one of which is microcephalin (Mcph1). Mcph1 prevents condensin II from associating with chromatin through interphase. Loss of Mcph1 induces chromosome hypercondensation; it is not clear to what extent this reorganization affects gene expression. In this study, we generated several mouse embryonic stem cell (mESC) lines with knockout of the Mcph1 gene and analyzed their gene expression profile. Gene Ontology analyses of differentially expressed genes (DEGs) after Mcph1 knockout revealed gene categories related to general metabolism and olfactory receptor function but not to cell cycle control previously described for Mcph1. We did not find a correlation between the DEGs and their frequency of lamina association. Thus, this evidence questions the hypothesis that Mcph1 knockout-mediated chromatin reorganization governs gene expression in mESCs. Among the negative effects of Mcph1 knockout, we observed numerous chromosomal aberrations, including micronucleus formation and chromosome fusion. This confirms the role of Mcph1 in maintaining genome integrity described previously. In our opinion, dysfunction of Mcph1 may be a kind of "Rosetta stone" for deciphering the function of condensin II in the interphase nucleus. Thus, the cell lines with knocked-out Mcph1 can be used to further study the influence of chromatin structural proteins on gene expression.

Aneuploidy in neoplasia: Single-cell data on 83,862 tumors.

Chromosomal aneuploidy, that is, numerical chromosome aberrations, is one of the molecular hallmarks of cancer. However, when neoplasms are studied with sequencing- and array-based approaches, chromosome numbers and ploidy states are typically inferred from bulk DNA data. Furthermore, published molecular estimates of neoplasia-associated aneuploidy often also include genomic imbalances resulting from various types of structural rearrangement, which likely result from other mechanisms than numerical chromosome aberrations. We thus analyzed chromosome numbers using single-cell cytogenetic data from 83,862 tumors, and show that both benign and malignant tumors are highly heterogeneous with regard to deviations from the normal, diploid state. Focusing on the chromosome numbers in 112 specific tumor types, defined by both exact morphologic diagnosis and organ location and from which data from ≥50 cases were available, we found two major clusters: one predominated by near-diploid neoplasms and one by neoplasms with extensive aneuploidy and one or more whole genome doublings. The former cluster included most benign solid tumors, myeloid neoplasms, and malignant gene fusion-associated solid tumors, whereas the latter was predominated by malignant solid tumors and lymphomas. For 16 malignant tumor types, the distribution of chromosome numbers could be compared to TCGA ploidy level data. Cytogenetic and molecular data correlated well, but the former indicates a higher level of clonal heterogeneity. The results presented here suggest shared pathogenetic mechanisms in certain tumor types and provide a reference for molecular analyses.

Prenatal diagnosis of fetuses with 15q11.2 BP1-BP2 microdeletion in the Chinese population: a seven-year single-center retrospective study

BackgroundThe 15q11.2 BP1-BP2 microdeletion syndrome is associated with developmental delays, language impairments, neurobehavioral disorders, and psychiatric complications. The aim of the present study was to provide prenatal and postnatal clinical data for 16 additional fetuses diagnosed with the 15q11.2 BP1-BP2 microdeletion syndrome in the Chinese population.MethodsA total of 5,789 pregnancy women that underwent amniocentesis were enrolled in the present study. Both karyotype analysis and chromosomal microarray analysis (CMA) were conducted on these subjects to detect chromosomal abnormalities and copy number variants (CNVs). Whole exome sequencing (WES) was performed to investigate sequence variants in subjects with clinical abnormalities after birth.ResultsSixteen fetuses with 15q11.2 BP1-BP2 microdeletion were identified in the present study, with a detection rate of 0.28% (16/5,789). The 15q11.2 BP1-BP2 microdeletion fragments ranged from 311.8 kb to 849.7 kb, encompassing the NIPA1, NIPA2, CYFIP1, and TUBGCP5 genes. The follow-up results regarding pregnancy outcomes showed that five cases opted for pregnancy termination, while the remaining cases continued with their pregnancies. Subsequent postnatal follow-up indicated that only one case with the 15q11.2 BP1-BP2 microdeletion displayed neurodevelopmental disorders, demonstrating an incomplete penetrance rate of 9.09% (1/11).ConclusionThe majority of fetuses with the 15q11.2 microdeletion exhibit typical features during early childhood, indicating a low penetrance and mild impact. Nonetheless, pregnancies involving fetuses with the 15q11.2 microdeletion require thorough prenatal counseling. Additionally, enhanced supervision and extended postnatal monitoring are warranted for those who choose to proceed with their pregnancies.

Single-Center Experience in Patients with Mixed Gonadal Dysgenesis.

Mixed gonadal dysgenesis (MGD) is an uncommon chromosomal Disorder of Sexual Development (DSD). There is insufficient information regarding clinical findings and growth patterns. This study aimed to provide more information about mixed gonadal dysgenesis, which has not yet been sufficiently defined. Data from 10 patients diagnosed with mixed gonadal dysgenesis were retrospectively reviewed. Clinical presentations, complaints at admission, imaging, genetic results, and treatments received by the patients were examined. Gonadal status and the gender of the patients were reared and evaluated by a multidisciplinary council decision. If received, growth hormone treatment doses and height gains were examined. The patients' ages at admission range from 6 months to 17.5 years. The median height SDS of the patients was -0.75 (2.73), the mean body weight SDS was -0.49 (±1.46), and the mean body mass index (BMI) SDS was 0.26 (±0.97). The complaints at admission varied, including ambiguous genitalia, short stature, and absence of menstruation. Some patients are completely in the female phenotype, while some are inadequately virilized male phenotype. External Masculinization Score (EMS) ranges from 1 to 6.5. The decision to raise 6 patients as female and 4 patients as male was made by a multidisciplinary council. Growth hormone treatment was administered to patients raised as female and diagnosed with short stature. The height SDS gain in treated patients was 0.42 (±0.49). Due to its rarity and varied clinical presentation, our knowledge about mixed gonadal dysgenesis is limited. Therefore, early diagnosis and individualized treatment plans are crucial for this patient group.

Maternal Exposure to Per- and Polyfluoroalkyl Substances and Offspring Chromosomal Abnormalities: The Japan Environment and Children's Study.

Although recent in vitro experimental results have raised the question of whether maternal exposure to per- and polyfluoroalkyl substances (PFAS) may be a potential environmental risk factor for chromosomal abnormalities, epidemiological studies investigating these associations are lacking. This study examined whether prenatal PFAS exposure is associated with a higher prevalence of chromosomal abnormalities among offspring. We used data from the Japan Environment and Children's Study, a nationwide birth cohort study, and employed logistic regression models to examine the associations between maternal plasma PFAS concentrations in the first trimester and the diagnosis of chromosomal abnormalities in all births (artificial abortions, miscarriages, stillbirths, and live births) up to 2 years of age. In addition, we examined associations with mixtures of PFAS using multipollutant models. The final sample consisted of 24,724 births with singleton pregnancies, of which 44 confirmed cases of chromosomal abnormalities were identified (prevalence: 17.8/10,000 births). When examined individually, exposure to perfluorononanoic acid (PFNA) and perfluorooctane sulfonic acid (PFOS) showed positive associations with any chromosomal abnormalities with age-adjusted odds ratios of 1.81 (95% CI: 1.26, 2.61) and 2.08 (95% CI: 1.41, 3.07) per doubling in concentration, respectively. These associations remained significant after Bonferroni correction, although they did not reach the adjusted significance threshold in certain sensitivity analyses. Furthermore, the doubling in all PFAS included as a mixture was associated with chromosomal abnormalities, indicating an age-adjusted odds ratio of 2.25 (95% CI: 1.34, 3.80), with PFOS as the predominant contributor, followed by PFNA, perfluoroundecanoic acid (PFUnA), and perfluorooctanoic acid (PFOA). The study findings suggested a potential association between maternal exposure to PFAS, particularly PFOS, and chromosomal abnormalities in offspring. However, the results should be interpreted cautiously, because selection bias arising from the recruitment of women in early pregnancy may explain the associations. https://doi.org/10.1289/EHP13617.

Klinefelter syndrome in a patient with double Y-autosomal translocation

Klinefelter syndrome is one of the most common chromosomal abnormalities and the most common genetic cause of male infertility. About 85 % of patients have 47,XXY karyotype, other patients have other non-mosaic and mosaic Klinefelter syndrome variants. We report a unique clinical case — Klinefelter syndrome patient with double Y autosomal translocation. The proband is a 15-year-old male patient (height 180 cm, weight 50 kg, normal IQ) who was admitted for cytogenetic examination and genetic counseling due to delayed puberty. He was diagnosed with testicular hypoplasia, hypergonadotropic hypogonadism, pituitary microadenoma and left-sided varicocele. The proband was born in a nonconsanguineous marriage after in vitro fertilization due to paternal male factor infertility. Cytogenetic analysis was performed on cultured peripheral blood lymphocytes using standard chromosome analysis with GTG staining and FISH analysis. Molecular analysis of the Y chromosome was performed by multiplex PCR. Complex cytogenetic examination revealed a 46,XX,der(Y) t(Y;15)(q12;q11.1),der(13)t(Y;13)(q12;p11.2),-15 karyotype in the proband. Molecular analysis showed that the proband is SRY positive; no microdeletion of the Y chromosome was found. The detected double Y autosomal translocation is a chromosomal abnormality independent of KS. The father of the proband is an oligozoospermic man with robertsonian translocation 13;15 — 45,XY,der(13;15)(q10;q10), the mother has a normal karyotype 46,XX. Apparently, the der(13) and der(Y) chromosomes result from abnormal meiotic recombination in paternal meiosis between the heterochromatic region Yq12 and the centromeric/pericentromeric heterochromatin of chromosomes 13 and 15 involved in the paternal robertsonian translocation, and Klinefelter syndrome is due to the presence of two X chromosomes in the karyotype in the presence of a derivative Y chromosome. The detected double Y-autosomal translocation is a chromosomal abnormality unrelated to Klinefelter syndrome, arising on the background of the paternal robertsonian translocation.

Comparative analysis of cyto-genotoxicity of zinc using the comet assay and chromosomal abnormality test.

In this study, the toxicity of the trace element zinc (Zn) in Allium cepa L. test material was examined. Toxicity was investigated in terms of physiological, cytogenetic, biochemical, and anatomical aspects. Germination percentage, root length, weight gain, mitotic index (MI), micronucleus (MN) frequency, chromosomal abnormalities (CAs), malondialdehyde (MDA), proline and chlorophyll levels, superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and meristematic cell damage were used as indicators of toxicity. Additionally, the comet test was used to measure the degree of DNA damage. Four groups of A. cepa bulbs-one for control and three for applications-were created. While the bulbs in the treatment groups were germinated with Zn at concentrations of 35, 70, and 140mg/L, the bulbs in the control group were germinated with tap water. Germination was carried out at room temperature for 72h and 144h. When the allotted time was over, the root tips and leaf samples were collected and prepared for spectrophotometric measurements and macroscopic-microscopic examinations. Consequently, Zn treatment led to significant reductions in physiological indicators such as weight gain, root length, and germination percentage. Zn exposure caused genotoxicity by decreasing the MI ratios and increasing the frequency of MN and CAs (p < 0.05). Zn promoted various types of CAs in root tip cells. The most observed of CAs was the sticky chromosome. Depending on the dose, Zn was found to cause an increase in tail lengths in comet analyses, which led to DNA damage. Exposure to Zn led to a significant decrease in chlorophyll levels and an increase in MDA and proline levels. It also promoted significant increases in SOD and CAT enzyme activities up to 70mg/L dose and statistically significant decreases at 140mg/L dose. Additionally, Zn exposure caused different types of anatomical damage. The most severe ones are epidermis and cortex cell damage. Besides, it was found that the Zn dose directly relates to all of the increases and decreases in physiological, cytogenetic, biochemical, and anatomical parameters that were seen as a result of Zn exposure. As a result, it has been determined that the Zn element, which is absolutely necessary in trace amounts for the continuation of the metabolic activities of the organisms, can cause toxicity if it reaches excessive levels.

Survival in Patients with Uveal Melanoma Is Linked to Genetic Variation at HERC2 Single Nucleotide Polymorphism rs12913832

Uveal melanoma (UM) is a rare disease, with the highest incidence in people with fair skin and light eyes. Eye color is largely genetically determined and is defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP related to prognosis. We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of 6 common eye color-related SNPs. Clinical and histopathologic tumor characteristics, tumor chromosome status, and patient survival were compared among patients with different genotypes. Three hundred ninety-two patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands. We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using 6 eye color SNPs from the HIrisPlex-S assay (Erasmus MC, Walsh lab). The genotypes extracted from the sequencing data were uploaded onto the HIrisPlexwebtool (https://hirisplex.erasmusmc.nl/) for eye color prediction. We tested the association of eye color SNPs with tumor characteristics and chromosome aberrations using Pearson's chi-square test and the Mann-Whitney U test and evaluated survival with Kaplan-Meier curves with the log-rank test and Cox regression. Uveal melanoma-related survival. Of 392 patients with analyzable genotype data, 307 patients (78%) were assigned blue eyes, 74 patients (19%) were assigned brown eyes, and 11 patients (3%) could not be assigned to either blue or brown. Patients with a genetically blue eye color showed worse survival (P= 0.04). This was related to 1 genotype: patients with the G/G genotype of rs12913832 (HERC2), which codes for blue eye color showed a worse prognosis (P= 0.017) and more often had high-risk tumors (monosomy of chromosome 3; P= 0.04) than in patients with an A/G or A/A genotype. The G/G genotype of rs12913832 (HERC2), which is related to blue eye color, not only is a genetic factor related to the risk of UM develop, but also is linked to a worse prognosis because of an association with a higher risk of a high-risk UM developing (carrying monosomy of chromosome 3). The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cytogenetic and Molecular Characteristics in Adult Hispanic Acute Myeloid Leukemia Patients From Puerto Rico.

The cytogenetic and molecular heterogeneity of acute myeloid leukemia (AML) is characterized as a contributing factor in the disparity of treatment outcomes and clinical outcomes seen among ethnic and racial groups. In this study, we have retrospectively evaluated the karyotypes of 800 adult Hispanic AML patients from Puerto Rico (PR). Acute promyelocytic leukemia with PML-RARA is the most common recurrent cytogenetic abnormality, compatible with previously published results. Among these AML patients, 163 patients had 21 gene panels performed. Twenty-six (15.95%) patients showed no detectable mutations, and 137 patients (84.05%) showed at least one mutation. Compared with previously published data from other examined Hispanic AML populations in the United States, mutational frequencies of these 21 genes, except for ASXL1, WT1, and KRAS,show no significant difference. This is the largest study to date about the landscape of cytogenetic and molecular abnormalities in Hispanic AML patients and a first report regarding the frequencies of these abnormalities in Puerto Rican Hispanic AML patients.

Prevalence and Association of Congenital Heart Disease with Hirschsprung’s Disease

Objective: Neurocristopathies play a role as pathogenesis of Hirschsprung’s disease and congenital heart diseases (CHDs). This study seeks to identify concomitant deformities, syndromes, and/or associations associated with Hirschsprung’s disease warrant evaluation for CHDs through echocardiography. Materials and Methods: A retrospective analysis was conducted on Hirschsprung’s disease patients at Siriraj Hospital between January 2006 and December 2022. Echocardiograms were performed when clinical symptoms, abnormal chest X-rays (CXR), desaturation, heart murmurs raised suspicions of cardiovascular anomalies. Results: Among 299 Hirschsprung’s disease patients, 43 (14.4%) exhibited CHDs. The sensitivity of CXR (n=268) and echocardiograms (n=51) in diagnosing CHDs was 48.8% and 100%, respectively. Predominant CHD presentations included patent ductus arteriosus (n=29), atrial septal defects (n=18), and ventricular septal defects (n=15). The presence of concomitant deformities, syndromes and/or associations associated with Hirschsprung’s disease significantly heightened the likelihood of concurrent CHDs (Odds ratio = 23.56, p &lt; 0.001). Patients with Hirschsprung’s disease and concomitant deformities (n=28) (excluding syndromic or chromosomal abnormalities) had 1.73 times the odds of CHDs (p = 0.262) compared to those without concomitant deformities. Patients with Hirschsprung’s disease and Down syndrome (n=34) exhibited 77.78 times higher odds of CHDs (p &lt; 0.001), while those with other syndromes and/or associations (n=6) had 13.03 times higher odds of CHDs (p = 0.005) compared to patients lacking these conditions. Conclusion: CHDs were identified in 14.4% of Hirschsprung’s disease patients. Echocardiograms should be selectively employed in Hirschsprung’s disease associated with Down syndrome, other syndromes, or concomitant deformities.

A Review of Arsenic Trioxide in the Treatment of Acute Promyelocytic Leukemia: Clinical Efficacy, Toxicity, and Future Directions

Acute promyelocytic leukemia (APL) is a severe and life-threatening form of leukemia characterized by unique genetic and chromosomal abnormalities, often leading to fatal complications such as hemorrhage and embolism. Arsenic trioxide (ATO) has become a key therapeutic agent for APL, achieving high remission rates, including in patients with relapsed disease, and offering advantages over other treatments such as bone marrow transplantation and all-trans retinoic acid (ATRA). This review examines the chemical and pharmacological properties of ATO, its mechanisms of action in APL treatment, and its clinical efficacy and toxicity based on studies conducted worldwide. Additionally, this review explores potential applications of ATO beyond APL and discuss future research directions to expand its therapeutic scope in clinical settings.

Advanced maternal age (AMA) and pregnancy: a feasible but problematic event.

This narrative review aimed to summarize all adverse outcomes of pregnancy in advanced maternal age (AMA) to assess the age of the mother as a potentially crucial risk factor. AMA refers to women older than 35 years. While expectations and the role of women in society have undergone significant changes today, the biology of aging remains unchanged. Various pathologic changes occur in the human body with age, including chronic noncommunicable diseases, as well as notable changes in reproductive organs, that significantly affect fertility. Despite substantial advancements in technology and medicine, pregnancy in AMA remains a formidable challenge. Although there are some advantages to postponing childbirth, they primarily relate to maternal maturity and economic stability. However, regrettably, there are also many adverse aspects of pregnancy at advanced ages. These include complications affecting both the mother and the fetus. Pregnants in AMA were more prone to suffer from gestational diabetes mellitus, preeclampsia, and eclampsia during pregnancy compared to younger women. In addition, miscarriages and ectopic pregnancies were more prevalent. Delivery was more frequently completed via cesarean section, and postpartum complications and maternal mortality were also higher. Unfortunately, there were also complications concerning the fetus, such as chromosomal abnormalities, premature birth, low birth weight, admission to the neonatal intensive care unit, and stillbirth.

Perinatal outcomes according to umbilical artery Doppler assessment among fetuses with congenital heart disease.

To evaluate a cohort of fetuses with congenital heart disease (CHD) who underwent serial umbilical artery (UA) Doppler surveillance and assess perinatal outcome according to UA Doppler assessment. A retrospective cohort study of singleton fetuses with CHD at a single academic center was performed between 2018 and 2020. Fetuses with a chromosomal abnormality or growth restriction were excluded. We compared fetuses with normal versus abnormal UA Doppler assessment at any time in pregnancy. Abnormal UA Doppler assessment was defined as decreased end diastolic flow, determined by an elevated systolic/diastolic ratio >95th percentile for gestational age, or absent/reversed end diastolic flow. Logistic regression assessed the odds of fetuses with CHD and abnormal UA Doppler assessment having a composite adverse perinatal (defined as fetal, neonatal, or infant death), adjusting for relevant covariates. We identified a cohort of 171 fetuses with CHD that met inclusion criteria. Of these, 154 (90%) had normal UA Doppler assessment and 17 (10%) had abnormal UA Doppler assessment throughout pregnancy. Maternal characteristics did not differ between groups except for maternal race and history of preeclampsia. There was no statistically significant difference in primary outcome between groups [14% (21/154) of fetuses with normal UA Doppler assessment had an adverse perinatal outcome compared to 24% (4/17) of those with abnormal UA Doppler assessment, p = 0.28]. UA Doppler assessment is unlikely to predict adverse perinatal outcome in normally grown, euploid singleton fetuses with CHD.

Performance evaluation of noninvasive prenatal testing on 24 chromosomes in a cohort of 118,969 pregnant women in Sichuan, China.

This study aimed to comprehensively analyze the detection capacity of non-invasive prenatal testing (NIPT) for chromosomal abnormalities of all 24 chromosomes, as well as high-risk indications for pregnancy and the fetal fraction, in a large cohort. We retrospectively enrolled 118,969 pregnant women who underwent NIPT at Sichuan Provincial Maternity and Child Health Care Hospital from March 2019 to June 2022. The sensitivity, specificity, positive predictive value, negative predictive value, and positive chromosomal abnormality rate were calculated. The fetal fraction based on gestational age, maternal body mass index, and number was examined. NIPT demonstrated > 99% sensitivity and specificity for almost all of the common trisomies (T21, T18, and T13), sex chromosomal aneuploidies, rare autosomal trisomies, and microdeletion/microduplication syndromes. Positive predictive values varied from 12.0% to 89.6%. Advanced maternal age was associated with an increased risk of three major aneuploidies. The fetal fraction was positively correlated with gestational age and negatively correlated with the maternal body mass index. NIPT can be used to effectively screen for chromosomal abnormalities across all 24 chromosomes. Advanced maternal age is a risk factor for high-risk pregnancy, and careful consideration of the fetal fraction is essential during NIPT.