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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 140 mg/L, the bulbs in the control group were germinated with tap water. Germination was carried out at room temperature for 72 h and 144 h. 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 70 mg/L dose and statistically significant decreases at 140 mg/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.

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Genetic counseling of mosaicism for a duplication due to partial trisomy in a cell line with 46 chromosomes associated with a normal cell line at amniocentesis remains difficult because mosaic duplication due to partial trisomy has been reported to be associated with either normal or abnormal phenotype in prenatal diagnosis. This article makes a comprehensive review of the reported cases of mosaicism for a duplication due to partial trisomy in a cell line with 46 chromosomes associated with a normal cell line at amniocentesis and various counseling issues such as culture artefact, cytogenetic discrepancy between cultured and uncultured amniocytes and among various tissues, perinatal progressive decrease of the abnormal cell line and a possible favorable fetal outcome. The information provided is useful for obstetricians and genetic counselors during genetic counseling of the parents who wish to keep the babies under such a circumstance.

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Genetic counseling of mosaic and non-mosaic tetrasomy 9p remains difficult because of the possible associated congenital abnormalities, cytogenetic discrepancy in various tissues, true-positive and false-positive diagnosis in non-invasive prenatal testing (NIPT), uniparental disomy (UPD) 9, tissue-limited mosaicism, perinatal progressive decrease of the aneuploid cell line, phenotypic normal carriers and possible favorable fetal outcome in the cases with mosaic tetrasomy 9p at amniocentesis. This article presents a comprehensive review of various counseling issues concerning mosaic and non-mosaic tetrasomy 9p at prenatal diagnosis, and the information provided is very useful for genetic counseling under such circumstances.

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Genetic counseling of mosaicism for balanced translocation with a normal cell line at amniocentesis is not difficult because most of the reported cases have normal phenotypes. However, genetic counseling of mosaicism for unbalanced translocation with a normal cell line at amniocentesis remains difficult because cases with mosaic unbalanced translocation with a normal cell line at prenatal diagnosis have been reported to be associated with either normal or abnormal phenotype. This article makes a comprehensive review of the reported cases of de novo or familial mosaic unbalanced translocation with a normal cell line and various counseling issues such as meiotic event, post-zygotic mitotic event, culture artefact, chimerism, uniparental disomy (UPD), jumping translocation, cytogenetic discrepancy between cultured and uncultured amniocytes and among various tissues, perinatal progressive decrease of the unbalanced translocation cell line and a possible favorable fetal outcome. The information provided is useful for obstetricians and genetic counselors during genetic counseling of the parents who wish to keep the babies under such a circumstance.

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Genetic counseling of mosaicism for a deletion due to partial monosomy in a cell line with 46 chromosomes associated with a normal cell line at amniocentesis remains difficult because mosaic deletion due to partial monosomy has been reported to be associated with either normal or abnormal phenotype in prenatal diagnosis. This article makes a comprehensive review of the reported cases of mosaicism for a deletion due to partial monosomy in a cell line with 46 chromosomes associated with a normal cell line at amniocentesis and various counseling issues such as culture artefact, cytogenetic discrepancy between cultured and uncultured amniocytes and among various tissues, perinatal progressive decrease of the abnormal cell line and a possible favorable fetal outcome. The information provided is useful for obstetricians and genetic counselors during genetic counseling of the parents who wish to keep the babies under such a circumstance.

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OBJECTIVE: We present low-level mosaic trisomy 14 at amniocentesis. CASE REPORT: A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET). Amniocentesis revealed a karyotype of 47,XX,+14 [4]/46,XX [27], consistent with 12.9% mosaicism for trisomy 14. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22, X) × 2 with no genomic imbalance. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 21 weeks of gestation and was offered expanded non-invasive prenatal testing (NIPT) which was positive for trisomy 14. At 24 weeks of gestation, she underwent repeat amniocentesis which revealed a karyotype of 47,XX,+14 [2]/46,XX [26], consistent with 7% mosaicism for trisomy 14. The parental karyotypes were normal. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance. Polymorphic marker analysis excluded uniparental disomy (UPD) 14. Interphase fluorescence in situ hybridization (FISH) analysis on 104 uncultured amniocytes detected no trisomy 14 cell. At 35 weeks of gestation, a 2315-g phenotypically normal baby was delivered. The umbilical cord and placenta had the karyotype of 46, XX (40/40 cells). aCGH analysis on the DNA extracted from peripheral blood and buccal mucosal cells at the age of three months revealed no genomic imbalance. The neonate was normal in phenotype and development during postnatal follow-ups. CONCLUSIONS: Low-level mosaic trisomy 14 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 14 cell line and a favorable fetal outcome.

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The role of cytogenetic abnormalities in non-systemic light chain amyloidosis monoclonal gammopathy of renal significance diseases still needs to be clarified. Bhutani et al. present the results of a study investigating the underlying plasma cell cytogenetic abnormalities in monoclonal immunoglobulin deposition disease (MIDD). The results show that translocation (11;14) is a common abnormality in MIDD and affects the presentation and outcomes. Commentary on: Bhutani et al. Translocation (11;14) is a common cytogenetic abnormality in clonal plasma cells in monoclonal immunoglobulin deposition disease. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19748.

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BACKGROUND: JAK2 mutation plays a clinically significant role in the pathogenesis of acute lymphoblastic leukemia (ALL) by enhancing its oncogenicity. The study aimed to characterize the molecular pathology and computational profile of the JAK2 mutation in an ALL cohort of Pakistani origin. METHODS: Ninety-three patients were enrolled in the current study. The disease diagnosis was confirmed via flow cytometry and karyotyping of bone marrow aspirate/blood. For the identification of causative gene variations and assessment of their potential impact, the JAK2 gene underwent direct sequencing and predictive computational and in silico structural analysis, respectively. RESULTS: JAK2 mutations were detected in 10 (11%) patients. All mutations were missense with 1 being frameshift. Most mutations showed a similar pattern to the wild type but p.N673H+p.V674L+p.C675W (AAD699), p.V674F (AAD704), and p.V674L (AAD705) exhibited statistically significant stability loss. The triple mutation displayed reduced stability both globally and locally. CONCLUSION: The pattern of gene defects in JAK2 in the studied cohort showed a disruption in proper folding behavior, evident from increased gyration values, resulting in the hypothesis that these mutations may cause structural alterations in the JAK2 protein that lead to disease progression.

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Stem cell therapy in cat patients needs a high quantity of mesenchymal stromal/stem cells (MSCs) requiring in vitro propagation under culture conditions which may potentially impact cellular characteristics and genetic stability. This study aimed to assess the in vitro characteristics and cytogenetic stability of cat adipose tissue-derived MSCs (cAT-MSCs). For this purpose, morphological features, clonogenic potential, and proliferative capacity of cAT-MSCs were assessed at passages 2 (P2), P4, and P6. Multipotency and immunophenotype were evaluated. Cytogenetic analyses were conducted up to P6. The cAT-MSCs exhibited a spindle-shaped morphology in early passages. The doubling time increased from 2.5 days at P2 to 9.4 at P4 and 10.5 at P6, accompanied by the observation of nuclear abnormalities such as cluster formation, karyorrhexis, karyolysis, and a decline in the mitotic index at P4. Cells demonstrated multipotency capacity and were CD45-, CD90+, and CD44+. Metaphase analysis at P2 and P4 revealed some indications of structural instability such as gaps, breaks, deletions, duplications, and early chromatid segregation, but these alterations did not show an increase across passages. In conclusion, cAT-MSCs decreased their proliferative capacity after P4, accompanied by morphological alterations and signs of structural instability.

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When an increased nuchal translucency (>3.00 mm) is observed during the echographic examination of a foetus in the first trimester of pregnancy, an increased risk of chromosomopathy is considered, and the pregnant woman is offered the possibility of an invasive investigation. Here, we focused our attention on prenatal diagnosis issues in cases of foetuses with cytogenetically balanced reciprocal translocations. We report the finding of a cytogenetically balanced, de facto genomically unbalanced translocation that poses a challenge in a case of prenatal diagnosis, changing the risk of Down syndrome in a Zellweger syndromic spectrum risk (PEX3 deletion). At term, a healthy baby was born. This case teaches that prenatal diagnosis in cases of foetuses at increased risk of chromosomal abnormality imperatively requires molecular investigation in addition to a morphological karyotype.

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RATIONALE AND OBJECTIVES: We explored the feasibility of using total tumor apparent diffusion coefficient (ttADC) histogram parameters to predict high-risk cytogenetic abnormalities (HRCA) in patients with multiple myeloma (MM) and compared the performance of an image prediction model based on these parameters with that of a combined prediction model based on these parameters and clinical indicators. METHODS: We retrospectively analyzed the parameters of the ttADC histogram based on whole-body diffusion-weighted images(WB-DWI) and clinical indicators in 92 patients with MM. The patients were divided into HRCA and non-HRCA groups according to the results of the fluorescence in situ hybridization. Logistic regression analysis was used to construct the image prediction and combined prediction models. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the performance of the models to identify HRCA. The DeLong test was used to compare the AUC differences of each prediction model. RESULTS: Logistic regression analysis results revealed that the ttADC histogram parameter, ttADC entropy < 7.959 (OR: 39.167; 95% confidence interval [CI]: 3.891-394.208; P < 0.05), was an independent risk factor for HRCA. The image prediction model consisted of ttADC entropy and ttADC SD. The combined prediction model included ttADC entropy along with patient clinical indicators such as biological sex and M protein percentage. The AUCs of the image prediction and combined prediction models were 0.739 and 0.811, respectively (P < .05). The image prediction model showed a sensitivity of 73.9% and a specificity of 68.1%. The combined prediction model showed 82.6% sensitivity and 72.5% specificity. CONCLUSIONS: Using ttADC histogram parameters based on WB-DWI images to predict HRCA in patients with MM is feasible, and combining ttADC parameters with clinical indicators can achieve better predictive performance.

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BACKGROUND: Differences in Sex Development (DSD) is a heterogeneous group of congenital alterations that affect inner and/or outer primary sex characters. Although these conditions do not represent a mortality risk, they can have a severe psycho-emotional impact if not appropriately managed. The genetic changes that can give rise to DSD are diverse, from chromosomal alterations to single base variants involved in the sexual development network. Epidemiological studies about DSD indicate a global frequency of 1:4500-5500, which can increase to 1:200-300, including isolated anatomical defects. To our knowledge, this study is the first to describe epidemiological and genetic features of DSD in a cohort of Mexican patients of a third-level care hospital. METHODS: Descriptive and retrospective cross-sectional study that analyzed DSD patients from 2015 to 2021 attended a Paediatric Hospital from Mexico City. RESULTS: One hundred one patients diagnosed with DSD were registered and grouped into different entities according to the Chicago consensus statement and the diagnosis defined by the multidisciplinary group. Of the total, 54% of them belong to the chromosomal DSD classification, 16% belongs to 46, XX and 30% of them belongs to the 46, XY classification. CONCLUSION: The frequency for chromosomal DSDs was consistent with the literature; however, we found that DSD 46, XY is more frequent in our cohort, which may be due to the age of the patients captured, the characteristics of our study population, or other causes that depend on the sample size.

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Purpose: Coal mining is a vital sector in Colombia, contributing significantly to the nation's economy and the development of its regions. However, despite its importance, it has led to a gradual decline in the health of mine workers and nearby residents. While the adverse health effects of open-pit coal mining on exposed individuals have been well-documented in Colombia and globally, studies investigating genetic damage in underground coal miners are lacking. Methods: The aim of our study was to evaluate chromosomal and genotoxic damage, in peripheral blood samples from a group of underground coal miners and residents of areas exposed to coal, in the town of Samacá, Boyacá-Colombia, and in a group of unexposed individuals by using banding and molecular cytogenetic techniques, as well as cytokinesis block micronucleus assays. Results: Our results suggest that occupational exposure to coal induces chromosomal and genotoxic damage in somatic cells of underground coal miners. Chromosomal and genotoxic damage is an important step in carcinogenesis and the development of many other diseases. Our findings provide valuable insights into the effects of coal dust exposure on chromosomal integrity and genetic stability. Conclusion: Our pilot study suggests that occupational exposure to coal induces chromosomal damage in underground coal miners, highlighting the importance of validating these findings with a larger sample size. Our results highlight the need to implement prevention and protection measures, as well as educational programs for underground coal miners. Characterizing and estimating exposure risks are extremely important for the safety of people exposed occupationally and environmentally to coal and its derivatives.

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Rationale and Objectives: Radiomics has demonstrated potential in predicting the cytogenetic status of multiple myeloma (MM). However, the role of single-sequence radiomic nomograms in predicting the high-risk cytogenetic (HRC) status of MM remains underexplored. This study aims to develop and validate radiomic nomograms based on fat-suppressed T2-weighted images (T2WI-FS) for predicting MM's HRC status, facilitating pre-treatment decision-making and prognostic assessment. Materials and methods: A cohort of 159 MM patients was included, comprising 71 HRC and 88 non-HRC cases. Regions of interest within the most significant tumor lesions on T2WI-FS images were manually delineated, yielding 1688 features. Fourteen radiomic features were selected using 10-fold cross-validation, employing methods such as variance thresholds, Student's t-test, redundancy analysis, and least absolute shrinkage and selection operator (LASSO). Logistic regression was utilized to develop three prediction models: a clinical model (model 1), a T2WI-FS radiomic model (model 2), and a combined clinical-radiomic model (model 3). Receiver operating characteristic (ROC) curves evaluated and compared the diagnostic performance of these models. Kaplan-Meier survival analysis and log-rank tests assessed the prognostic value of the radiomic nomograms. Results: Models 2 and 3 demonstrated significantly greater diagnostic efficacy compared to model 1 (p < 0.05). The areas under the ROC curve for models 1, 2, and 3 were as follows: training set-0.650, 0.832, and 0.846; validation set-0.702, 0.730, and 0.757, respectively. Kaplan-Meier survival analysis indicated comparable prognostic values between the radiomic nomogram and MM cytogenetic status, with log-rank test results (p < 0.05) and concordance indices of 0.651 and 0.659, respectively; z-score test results were not statistically significant (p = 0.153). Additionally, Kaplan-Meier analysis revealed that patients in the non-HRC group, low-RS group, and aged ≤ 60 years exhibited the longest overall survival, while those in the HRC group, high-RS group, and aged > 60 years demonstrated the shortest overall survival (p = 0.004, Log-rank test). Conclusions: Radiomic nomograms are capable of predicting the HRC status in MM. The cytogenetic status, radiomics model Rad score, and age collectively influence the overall survival of MM patients. These factors potentially contribute to pre-treatment clinical decision-making and prognostic assessment.

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Karuna JhaBackground Multiple myeloma is a cytogenetically heterogeneous, evolving, and incurable disease. Differences in prevalence of myeloma already exist in Indian subcontinent as compared with Western world countries. This study attempts to investigate differences in incidence of cytogenetic abnormalities (CA) in Eastern Indian patients and study differences in incidence with respect to age and gender. Materials and Methods Interphase fluorescence in situ hybridization (FISH) was applied on purified plasma cells of 280 newly diagnosed myeloma cases using specific probes. Statistical Analysis Data was analyzed using SPSS software version 25. Results Note that 51.07% patients were FISH positive. Del13q was the most common CA. Significant association of del 13q with t(4;14), del 17p, and gain of 1q was seen. The frequencies of FISH positive and negative groups differed in the different age groups; higher number of cases in 41 to 50 years group in FISH positive group ( p < 0.05) and lower number of cases in FISH positive group in 61 to 70 years ( p < 0.05) as compared with FISH negative group. Del 17p had higher number of cases in age group 41 to 50 years and 51 to 60 years as compared with other age groups. Incidence of t(11;14) was in 5th to 7th decade while del 13q and t(4;14) had the widest range of age at presentation. Gender disparities were seen in high-risk cytogenetics like del 17p and 1q gain. Conclusion The differences in incidence rate of CAs per se in myeloma cases diagnosed in Indian subcontinent and the differences in incidence with respect to age and gender warrant further multicentric studies.

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Acute promyelocytic leukemia is a rare form of acute myeloid leukemia in which immature promyelocytes abnormally proliferate in the bone marrow. In most cases, the disease is characterised by the translocation t(15;17) (q24;q21), which causes the formation of PML::RARA, an oncogenic fusion protein responsible for blocking myeloid differentiation and survival advantage. Here, we present a case of acute promyelocytic leukemia with two unusual features: basophilic differentiation and a three-way translocation involving chromosomes 12, 15 and 17. In the few cases reported, basophilic differentiation was associated with a poor prognosis. In contrast, our patient responded promptly to the standard treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) and obtained complete remission. To our knowledge, this is the first report of basophilic acute promyelocytic leukemia with the three-way translocation t(12;17;15) (p13; q24;q21).

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INTRODUCTION: Acute promyelocytic leukemia (APL) is genetically characterized by the fusion of promyelocytic leukemia (PML) gene with retinoic acid receptor alpha (RARα) resulting from a t(15;17)(q24;q21) chromosomal translocation. An infrequent but recurrent finding in APL is the formation of an isochromosome of the derivative chromosome 17; ider(17)(q10)t(15;17) or ider(17q). This rearrangement in APL results in an additional copy of the PML-RARα fusion gene as well as loss of 17p/TP53. Due to the infrequent occurrence of the ider(17q), the prognostic impact of this genetic finding is not well known. Case Presentation(s): Here, we describe the clinical characteristics and outcomes of our case series of 5 patients with ider(17q) APL treated at the University of Maryland and Johns Hopkins University. CONCLUSION: In our series, patients with APL with ider(17q) did not have a worse prognosis.

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BACKGROUND: There are no studies assessing the evolution and patterns of genetic studies performed at diagnosis in acute myeloid leukemia (AML) patients. Such studies could help to identify potential gaps in our present diagnostic practices, especially in the context of increasingly complex procedures and classifications. METHODS: The REALMOL study (NCT05541224) evaluated the evolution, patterns, and clinical impact of performing main genetic and molecular studies performed at diagnosis in 7285 adult AML patients included in the PETHEMA AML registry (NCT02607059) between 2000 and 2021. RESULTS: Screening rates increased for all tests across different time periods (2000-2007, 2008-2016, and 2017-2021) and was the most influential factor for NPM1, FLT3-ITD, and next-generation sequencing (NGS) determinations: NPM1 testing increased from 28.9% to 72.8% and 95.2% (p < .001), whereas FLT3-ITD testing increased from 38.1% to 74.1% and 95.9% (p < .0001). NGS testing was not performed between 2000-2007 and only reached 3.5% in 2008-2016, but significantly increased to 72% in 2017-2021 (p < .001). Treatment decision was the most influential factor to perform karyotype (odds ratio [OR], 6.057; 95% confidence interval [CI], 4.702-7.802), and fluorescence in situ hybridation (OR, 2.273; 95% CI, 1.901-2.719) studies. Patients ≥70 years old or with an Eastern Cooperative Oncology Group ≥2 were less likely to undergo these diagnostic procedures. Performing genetic studies were associated with a favorable impact on overall survival, especially in patients who received intensive chemotherapy. CONCLUSIONS: This unique study provides relevant information about the evolving landscape of genetic and molecular diagnosis for adult AML patients in real-world setting, highlighting the increased complexity of genetic diagnosis over the past 2 decades.

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Optical genome mapping (OGM) has generated excitement following decades of research and development. Now, commercially available technical platforms have been used to compare various other cytogenetic and cytogenomic technologies, including karyotype, microarrays, and DNA sequencing, with impressive results. In this chapter, using OGM as a case study, we advocate for a new trend in future cytogenomics, emphasizing the power of machine automation to deliver higher-quality cytogenomic data. By briefly discussing OGM, along with its major advantages and limitations, we underscore the importance of karyotype-based genomic research, from both a theoretical framework and a new technology perspective. We also call for the encouragement of further technological platform development for the future of cytogenetics and cytogenomics.

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