Comparative analysis of the yields of dicentrics and chromosomal translocations.

PURPOSE: Chromosomal dicentrics and translocations are commonly employed as biomarkers to estimate radiation doses. The main goal of this article is to perform a comparative analysis of yields of both types of aberrations. The objective is to determine if there are relevant distinctions between both yields, allowing for a comprehensive assessment of their respective suitability and accuracy in the estimation of radiation doses. MATERIALS AND METHODS: The analysis involved data from a partial-radiation simulation study with the calibration data obtained through two scoring methods: conventional and PAINT modified. Subsequently, a Bayesian bivariate zero-inflated Poisson model was employed to compare the posterior marginal density of the mean of dicentrics and translocations and assess the differences between them. RESULTS: When employing the conventional method of scoring, the findings indicate that there is no notable disparity between the yield of observed translocations and dicentrics. However, when utilizing the PAINT modified method, a notable discrepancy is observed for higher doses, indicating a relevant difference in the mean number of the two types of aberrations. CONCLUSIONS: The choice of scoring method significantly influences the analysis of radiation-induced aberrations, especially when distinguishing between complex and simple chromosomal formations. Further research and analysis are necessary to gain a deeper understanding of the factors and mechanisms impacting the formation of dicentrics and translocations.

A 12-year Life History of a Girl with Profound Intellectual Disability and Leukoencephalopathy: A Rare Clinical Presentation of X Chromosome Pentasomy.

This paper presents a unique 12-year case analysis of a girl with Penta-X syndrome, a chromosomal abnormality characterized by five X chromosomes instead of the normal two in healthy women. Pentasomy of X is a genetic, but not a hereditary disease affecting only women. Our patient demonstrated delayed mental, speech, and motor development along with physical anomalies such as craniofacial deformities, and eye pathology and was diagnosed with pentasomy of the X chromosome at the age of 3 after a cytogenetic examination. She developed epileptic seizures at the age of nine. Magnetic resonance imaging(MRI) revealed leukoencephalopathy with ventriculomegaly. The peculiarity of this observation is that the polysomy 49, XXXXX detected in the patient is characterized by a typical phenotypic presentation combined with demyelinating leukoencephalopathy, which has not been a typical feature of the disorder.

The New Era of Cancer Cytogenetics and Cytogenomics.

The promises of the cancer genome sequencing project, combined with various -omics technologies, have raised questions about the importance of cancer cytogenetic analyses. It is suggested that DNA sequencing provides high resolution, speed, and automation, potentially replacing cytogenetic testing. We disagree with this reductionist prediction. On the contrary, various sequencing projects have unexpectedly challenged gene theory and highlighted the importance of the genome or karyotype in organizing gene network interactions. Consequently, profiling the karyotype can be more meaningful than solely profiling gene mutations, especially in cancer where karyotype alterations mediate cellular macroevolution dominance. In this chapter, recent studies that illustrate the ultimate importance of karyotype in cancer genomics and evolution are briefly reviewed. In particular, the long-ignored non-clonal chromosome aberrations or NCCAs are linked to genome or chromosome instability, genome chaos is linked to genome reorganization under cellular crisis, and the two-phased cancer evolution reconciles the relationship between genome alteration-mediated punctuated macroevolution and gene mutation-mediated stepwise microevolution. By further synthesizing, the concept of karyotype coding is discussed in the context of information management. Altogether, we call for a new era of cancer cytogenetics and cytogenomics, where an array of technical frontiers can be explored further, which is crucial for both basic research and clinical implications in the cancer field.

Tracking Karyotype Changes in Treatment-Induced Drug-Resistant Evolution.

Karyotype coding, which encompasses the complete chromosome sets and their topological genomic relationships within a given species, encodes system-level information that organizes and preserves genes' function, and determines the macroevolution of cancer. This new recognition emphasizes the crucial role of karyotype characterization in cancer research. To advance this cancer cytogenetic/cytogenomic concept and its platforms, this study outlines protocols for monitoring the karyotype landscape during treatment-induced rapid drug resistance in cancer. It emphasizes four key perspectives: combinational analyses of phenotype and karyotype, a focus on the entire evolutionary process through longitudinal analysis, a comparison of whole landscape dynamics by including various types of NCCAs (including genome chaos), and the use of the same process to prioritize different genomic scales. This protocol holds promise for studying numerous evolutionary aspects of cancers, and it further enhances the power of karyotype analysis in cancer research.

Characterizing Chemotherapy/Radiotherapy-Induced Genome Chaos in Hodgkin's Lymphoma Patients Using M-FISH.

Hodgkin lymphoma (HL) is one of the most common lymphomas, with an incidence of 3 per 100,000 persons. Current treatment uses a cocktail of genotoxic agents, including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), along with or without radiotherapy. This treatment regimen has proved to be efficient in killing cancer cells, resulting in HL patients having a survival rate of >90% cancer-free survival at five years. However, this therapy does not have a specific cell target, and it can induce damage in the genome of non-cancerous cells. Previous studies have shown that HL survivors often exhibit karyotypes characterized by complex chromosomal abnormalities that are difficult to analyze by conventional banding. Multicolor fluorescence in situ hybridization (M-FISH) is a powerful tool to analyze complex karyotypes; we used M-FISH to investigate the presence of chromosomal damage in peripheral blood lymphocytes from five healthy individuals and five HL patients before, during, and one year after anti-cancer treatment. Our results show that this anti-cancer treatment-induced genomic chaos that persists in the hematopoietic stem cells from HL patients one year after finishing therapy. This chromosomal instability may play a role in the occurrence of second primary cancers that are observed in 10% of HL survivors. This chapter will describe a protocol for utilizing M-FISH to study treatment-induced genome chaos in Hodgkin's lymphoma (HL) patients, following a brief discussion.

The Digital World of Cytogenetic and Cytogenomic Web Resources.

The dynamic growth of technological capabilities at the cellular and molecular level has led to a rapid increase in the amount of data on the genes and genomes of organisms. In order to store, access, compare, validate, classify, and understand the massive data generated by different researchers, and to promote effective communication among research communities, various genome and cytogenetic online databases have been established. These data platforms/resources are essential not only for computational analyses and theoretical syntheses but also for helping researchers select future research topics and prioritize molecular targets. Furthermore, they are valuable for identifying shared recurrent genomic patterns related to human diseases and for avoiding unnecessary duplications among different researchers. The website interface, menu, graphics, animations, text layout, and data from databases are displayed by a front end on the screen of a monitor or smartphone. A database front-end refers to the user interface or application that enables accessing tabular, structured, or raw data stored in the database. The Internet makes it possible to reach a greater number of users around the world and gives them quick access to information stored in databases. The number of ways of presenting this data by front-ends increases as well. This requires unifying the ways of operating and presenting information by front-ends and ensuring contextual switching between front-ends of different databases. This chapter aims to present selected cytogenetic and cytogenomic Internet resources in terms of obtaining the needed information and to indicate how to increase the efficiency of access to stored information. Through a brief introduction of these databases and by providing examples of their usage in cytogenetic analyses, we aim to bridge the gap between cytogenetics and molecular genomics by encouraging their utilization.

Modelling Heterogeneous Anomalous Dynamics of Radiation-Induced Double-Strand Breaks in DNA during Non-Homologous End-Joining Pathway.

The process of end-joining during nonhomologous repair of DNA double-strand breaks (DSBs) after radiation damage is considered. Experimental evidence has revealed that the dynamics of DSB ends exhibit subdiffusive motion rather than simple diffusion with rare directional movement. Traditional models often overlook the rare long-range directed motion. To address this limitation, we present a heterogeneous anomalous diffusion model consisting of subdiffusive fractional Brownian motion interchanged with short periods of long-range movement. Our model sheds light on the underlying mechanisms of heterogeneous diffusion in DSB repair and could be used to quantify the DSB dynamics on a time scale inaccessible to single particle tracking analysis. The model predicts that the long-range movement of DSB ends is responsible for the misrepair of DSBs in the form of dicentric chromosome lesions.

Biologic and Clinical Characteristics of Isochromosome der(17)(q10)t(15;17) in Acute Promyelocytic Leukemia.

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.

Congenital hand difference associated with 12q13.13 microdeletion.

We report the case of a 15-year-old boy with a de novo chromosomal deletion in the 12q13.13 region, presenting with congenital hand difference. This case emphasizes the clinical significance of recognizing such genetic anomalies and their implications.

Genotoxic and Anti-Genotoxic Potential of Hydrosols from Water-Steam Distillation of Oil-Bearing Roses Rosa centifolia L. and Rosa gallica L. from Bulgaria.

Rosa centifolia L. and Rosa gallica L. (Rosaceae) are grown as raw materials for valuable essential oils and hydrosols. There are scarce data about the biological activities and the genoprotective potential of the hydrosols of these roses. The aim of the study was to provide information on their cytotoxic/genotoxic activity and anti-cytotoxic/anti-genotoxic capacity against mutagenic N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The evaluation was performed using classical tests for chromosomal aberrations and micronuclei in the higher plant Hordeum vulgare and human lymphocyte test systems. The experimental schemes included combined hydrosol and mutagen treatment. Both hydrosols (6, 14, 20%) had no cytotoxic effect on barley and showed low genotoxicity in both test systems as the injuries were enhanced to a lesser extent compared to the controls. Lymphocytes were more susceptible than H. vulgare. Under the conditions of combined treatment, it was found that the two hydrosols possessed good anti-cytotoxic and anti-genotoxic potential against MNNG. Both rose products exerted genoprotective potential to a similar extent, decreasing the frequencies of aberrations in chromosomes and micronuclei to a significant degree in both types of cells when non-toxic concentrations of hydrosols were applied before MNNG. This was performed both with and without any inter-treatment time. The observed cytoprotective/genoprotective potential suggests that these hydrosols are promising for further application in phytotherapy and medicine.

Gain-Type Aneuploidies Influence the Burden of Selective Long Non-Coding Transcripts in Colorectal Cancer.

Chromosomal instability is a hallmark of colorectal carcinogenesis and produces an accumulation of different forms of aneuploidies or broad copy number aberrations. Colorectal cancer is characterized by gain-type broad copy number aberrations, specifically in Chr20, Chr8q, Chr13 and Chr7, but their roles and mechanisms in cancer progression are not fully understood. It has been suggested that broad copy number gains might contribute to tumor development through the so-called caricature transcriptomic effect. We intend to investigate the impact of broad copy number gains on long non-coding RNAs' expression in colorectal cancer, given their well-known role in oncogenesis. The influence of such chromosomal aberrations on lncRNAs' transcriptome profile was investigated by SNP and transcriptome arrays in our series of colorectal cancer samples and cell lines. The correlation between aneuploidies and transcriptomic profiles led us to obtain a class of Over-UpT lncRNAs, which are transcripts upregulated in CRC and further overexpressed in colon tumors bearing specific chromosomal aberrations. The identified lncRNAs can contribute to a wide interaction network to establish the cancer driving effect of gain-type aneuploidies.

Comprehensive preimplantation genetic testing for balanced insertional translocation carriers.

BACKGROUND: Balanced insertional translocations (BITs) can increase the risk of infertility, recurrent miscarriages or neonatal birth defects due to chromosomal imbalances in gametes. However, studies on preimplantation genetic testing (PGT) for patients carrying BITs are inadequate. METHODS: A preimplantation genetic genotyping and haplotype analysis approach was developed and implemented in this study. Genome-wide SNP genotyping was performed, followed by core family-based haplotype analysis. The balanced insertion segments in euploid embryos were inferred from the haplotypes inherited from the carrier parent. RESULTS: A total of 10 BIT carrier couples were enrolled in our study. 15 in vitro fertilisation cycles were conducted, resulting in 73 blastocysts biopsied and subjected to PGT analysis. Among these, 20 blastocysts displayed rearrangement-related imbalances, 13 exhibited de novo aneuploidies, 15 presented a complex anomaly involving both imbalances and additional aneuploidies, while 25 were euploid. Within the euploid embryos, 12 were balanced carrier embryos and 13 were non-carrier embryos. To date, eight non-carrier and one carrier embryos have been transferred, resulting in seven clinical pregnancies. All pregnancies were recommended to perform prenatal diagnosis, our date revealed complete concordance between fetal genetic testing results and PGT results. Presently, five infants have been born from these pregnancies, and two pregnancies are still ongoing. CONCLUSION: The proposed method facilitates comprehensive chromosome screening and the concurrent identification of balanced insertions or normal karyotypes in embryos. This study offers an effective and universally applicable strategy for BIT carriers to achieve a healthy pregnancy and prevent the transmission of BITs to their offspring.

Pan-neuronal expression of human mutant SOD1 in Drosophila impairs survival and motor performance, induces early neuroinflammation and chromosome aberrations.

Several mutations in the SOD1 gene encoding for the antioxidant enzyme Superoxide Dismutase 1, are associated with amyotrophic lateral sclerosis, a rare and devastating disease characterized by motor neuron degeneration and patients' death within 2-5 years from diagnosis. Motor neuron loss and related symptomatology manifest mostly in adult life and, to date, there is still a gap of knowledge on the precise cellular and molecular events preceding neurodegeneration. To deepen our awareness of the early phases of the disease, we leveraged two Drosophila melanogaster models pan-neuronally expressing either the mutation A4V or G85R of the human gene SOD1 (hSOD1A4V or hSOD1G85R). We demonstrate that pan-neuronal expression of the hSOD1A4V or hSOD1G85R pathogenic construct impairs survival and motor performance in transgenic flies. Moreover, protein and transcript analysis on fly heads indicates that mutant hSOD1 induction stimulates the glial marker Repo, up-regulates the IMD/Toll immune pathways through antimicrobial peptides and interferes with oxidative metabolism. Finally, cytological analysis of larval brains demonstrates hSOD1-induced chromosome aberrations. Of note, these parameters are found modulated in a timeframe when neurodegeneration is not detected. The novelty of our work is twofold: we have expressed for the first time hSOD1 mutations in all neurons of Drosophila and confirmed some ALS-related pathological phenotypes in these flies, confirming the power of SOD1 mutations in generating ALS-like phenotypes. Moreover, we have related SOD1 pathogenesis to chromosome aberrations and antimicrobial peptides up-regulation. These findings were unexplored in the SOD1-ALS field.

Systematic reanalysis of copy number losses of uncertain clinical significance.

BACKGROUND: Reanalysis of exome/genome data improves diagnostic yield. However, the value of reanalysis of clinical array comparative genomic hybridisation (aCGH) data has never been investigated. Case-by-case reanalysis can be challenging in busy diagnostic laboratories. METHODS AND RESULTS: We harmonised historical postnatal clinical aCGH results from ~16 000 patients tested via our diagnostic laboratory over ~7 years with current clinical guidance. This led to identification of 37 009 copy number losses (CNLs) including 33 857 benign, 2173 of uncertain significance and 979 pathogenic. We found benign CNLs to be significantly less likely to encompass haploinsufficient genes compared with the pathogenic or CNLs of uncertain significance in our database. Based on this observation, we developed a reanalysis pipeline using up-to-date disease association data and haploinsufficiency scores and shortlisted 207 CNLs of uncertain significance encompassing at least one autosomal dominant disease-gene associated with haploinsufficiency or loss-of-function mechanism. Clinical scientist reviews led to reclassification of 15 CNLs of uncertain significance as pathogenic or likely pathogenic. This was ~0.7% of the starting cohort of 2173 CNLs of uncertain significance and 7.2% of 207 shortlisted CNLs. The reclassified CNLs included first cases of CNV-mediated disease for some genes where all previously described cases involved only point variants. Interestingly, some CNLs could not be reclassified because the phenotypes of patients with CNLs seemed distinct from the known clinical features resulting from point variants, thus raising questions about accepted underlying disease mechanisms. CONCLUSIONS: Reanalysis of clinical aCGH data increases diagnostic yield.

Persons chronically exposed to low doses of ionizing radiation: A cytogenetic dosimetry study.

The dosimetry and control of exposure for individuals chronically exposed to ionizing radiation are important and complex issues. Assessment may be optimized by evaluating individual adaptation and radiosensitivity, but it is not possible for a single model to account for all relevant parameters. Our goal was to develop approaches for the calculation of doses for persons chronically exposed to ionizing radiation, taking their radiosensitivities into consideration. On the basis of ex vivo radiation of blood samples, dose-effect models were constructed for dose ranges 0.01-2.0 and 0.01-0.4 Gy, using different cytogenetic criteria. The frequencies of "dicentric chromosomes and rings" at low doses are too low to have predictive value. The different responses of subjects to radiation made it possible to categorize them according to their radiosensitivities and to generate separate dose-effect curves for radiosensitive, average, and radioresistant individuals, reducing the amount of error in retrospective dosimetry.

Acute myeloid leukemia with rare recurring translocations-an overview of the entities included in the international consensus classification.

Two different systems exist for subclassification of acute myeloid leukemia (AML); the World Health Organization (WHO) Classification and the International Consensus Classification (ICC) of myeloid malignancies. The two systems differ in their classification of AML defined by recurrent chromosomal abnormalities. One difference is that the ICC classification defines an AML subset that includes 12 different genetic abnormalities that occur in less than 4% of AML patients. These subtypes exhibit distinct clinical traits and are associated with treatment outcomes, but detailed description of these entities is not easily available and is not described in detail even in the ICC. We searched in the PubMed database to identify scientific publications describing AML patients with the recurrent chromosomal abnormalities/translocations included in this ICC defined patient subset. This patient subset includes AML with t(1;3)(p36.3;q21.3), t(3;5)(q25.3;q35.1), t(8;16)(p11.2;p13.3), t(1;22)(p13.3;q13.1), t(5;11)(q35.2;p15.4), t(11;12)(p15.4;p13.3) (involving NUP98), translocation involving NUP98 and other partner, t(7;12)(q36.3;p13.2), t(10;11)(p12.3;q14.2), t(16;21)(p11.2;q22.2), inv(16)(p13.3q24.3) and t(16;21)(q24.3;q22.1). In this updated review we describe the available information with regard to frequency, biological functions of the involved genes and the fusion proteins, morphology/immunophenotype, required diagnostic procedures, clinical characteristics (including age distribution) and prognostic impact for each of these 12 genetic abnormalities.

Monitoring Genomic Structural Rearrangements Resulting from Gene Editing.

The cytogenomics-based methodology of directional genomic hybridization (dGH) enables the detection and quantification of a more comprehensive spectrum of genomic structural variants than any other approach currently available, and importantly, does so on a single-cell basis. Thus, dGH is well-suited for testing and/or validating new advancements in CRISPR-Cas9 gene editing systems. In addition to aberrations detected by traditional cytogenetic approaches, the strand specificity of dGH facilitates detection of otherwise cryptic intra-chromosomal rearrangements, specifically small inversions. As such, dGH represents a powerful, high-resolution approach for the quantitative monitoring of potentially detrimental genomic structural rearrangements resulting from exposure to agents that induce DNA double-strand breaks (DSBs), including restriction endonucleases and ionizing radiations. For intentional genome editing strategies, it is critical that any undesired effects of DSBs induced either by the editing system itself or by mis-repair with other endogenous DSBs are recognized and minimized. In this paper, we discuss the application of dGH for assessing gene editing-associated structural variants and the potential heterogeneity of such rearrangements among cells within an edited population, highlighting its relevance to personalized medicine strategies.

M-FISH evaluation of chromosome aberrations to examine for historical exposure to ionising radiation due to participation at British nuclear test sites.

Veterans of the British nuclear testing programme represent a population of ex-military personnel who had the potential to be exposed to ionising radiation through their participation at nuclear testing sites in the 1950s and 1960s. In the intervening years, members of this population have raised concerns about the status of their health and that of their descendants, as a consequence. Radiation dose estimates based on film badge measurements of external dose recorded at the time of the tests suggest any exposure to be limited for the majority of personnel, however, only ∼20% of personnel were monitored and no measurement for internalised exposure are on record. Here, to in-part address families concerns, we assay for chromosomal evidence of historical radiation exposure in a group of aged nuclear test (NT) veterans, using multiplexin situhybridisation (M-FISH), for comparison with a matched group of veterans who were not present at NT sites. In total, we analysed 9379 and 7698 metaphase cells using M-FISH (24-colour karyotyping) from 48 NT and 38 control veteran samples, representing veteran servicemen from the army, Royal Airforce and Royal Navy. We observed stable and unstable simple- and complex-type chromosome aberrations in both NT and control veterans' samples, however find no significant difference in yield of any chromosome aberration type between the two cohorts. We do observe higher average frequencies of complex chromosome aberrations in a very small subset of veterans previously identified as having a higher potential for radiation exposure, which may be indicative of internalised contamination to long-lived radionuclides from radiation fallout. By utilising recently published whole genome sequence analysis data of a sub-set of the same family groups, we examined for but found no relationship between paternal chromosome aberration burden, germline mutation frequency and self-reported concerns of adverse health in family members, suggesting that the previously reported health issues by participants in this study are unlikely to be associated with historical radiation exposure. We did observe a small number of families, representing both control and NT cohorts, showing a relationship between paternal chromosome aberrations and germline mutation sub-types which should be explored in future studies. In conclusion, we find no cytogenetic evidence of historical radiation exposure in the cohort of nuclear veterans sampled here, offering reassurance that attendance at NTs sites by the veterans sampled here, was not associated with significant levels of exposure to radiation.

Experience of copy number variation sequencing applied in spontaneous abortion.

PURPOSE: We evaluated the value of copy number variation sequencing (CNV-seq) and quantitative fluorescence (QF)-PCR for analyzing chromosomal abnormalities (CA) in spontaneous abortion specimens. METHODS: A total of 650 products of conception (POCs) were collected from spontaneous abortion between April 2018 and May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. The clinical features of the patients were recorded. RESULTS: Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, of which 217 (33.4%) were autosomal trisomies, 42(6.5%) were chromosomal monosomies and 40 (6.2%) were pathogenic CNVs (pCNVs). Chromosomal trisomy occurs mainly on chromosomes 15, 16, 18, 21and 22. Monosomy X was not associated with the maternal or gestational age. The frequency of chromosomal abnormalities in miscarriages from women with a normal live birth history was 55.3%; it was 54.4% from women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and with ≥ 2 previous miscarriages regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 and 30-34 years (P < 0.05). CONCLUSION: Chromosomal abnormalities are the most common cause of pregnancy loss, and maternal and gestational ages are strongly associated with fetal autosomal trisomy aberrations. Embryo chromosomal examination is recommended regardless of the gestational age, modes of conception or previous abortion status.

Maternal age and the risk of fetal aneuploidy: A nationwide cohort study of more than 500 000 singleton pregnancies in Denmark from 2008 to 2017.

INTRODUCTION: In this register-based study of pregnancies in Denmark, we assessed the associations between maternal age and the risk of fetal aneuploidies (trisomy 21, trisomy 18, trisomy 13, triploidy, monosomy X and other sex chromosome aberrations). Additionally, we aimed to disentangle the maternal age-related effect on fetal aneuploidies by cases with translocation trisomies and mosaicisms. MATERIAL AND METHODS: We followed a nationwide cohort of 542 375 singleton-pregnant women attending first trimester screening in Denmark between 2008 and 2017 until delivery, miscarriage or termination of pregnancy. We used six maternal age categories and retrieved information on genetically confirmed aneuploidies of the fetus and infant from the national cytogenetic register. RESULTS: We confirmed the known associations between advanced maternal age and higher risk of trisomy 21, 18, 13 and other sex chromosome aberrations, especially in women aged ≥35 years, whereas we found no age-related associations with triploidy or monosomy X. Cases with translocation trisomies and mosaicisms did not influence the overall reported association between maternal age and aneuploidies. CONCLUSION: This study provides insight into the accurate risk of fetal aneuploidies that pregnant women of advanced ages encounter.