Chromosomal Aberrations Research Articles

Umbilical Cord Abnormalities.

The umbilical cord is the connection between mother and fetus through which gases and nutrients are exchanged. It's remarkable structure allows for freedom of movement while providing a cushioned, protected conduit from mother to fetus. Fetal development and survival are dependent upon the umbilical cord. This article reviews abnormalities of the umbilical cord that can be seen with structural and chromosomal abnormalities and altered umbilical cord flow associated with fetal growth restriction and poor pregnancy outcomes.

Transcriptomic clustering of chronic lymphocytic leukemia: molecular subtypes based on Bruton’s tyrosine kinase expression levels

Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression. We hypothesized that transcriptome and proteome may identify functional omics associated with CLL nosology. As a test cohort, we utilized publicly available treatment-naïve CLL transcriptomics data (n = 130) and did consensus clustering that identified BTK-expression-based clusters. The BTK-High and BTK-Low clusters were validated in public and our in-house databases (n = >550 CLL patients). To associate with functional relevance, we took samples from 151 previously treated patient with CLL and analyzed them using RNA sequencing and reverse-phase protein array. Transcript levels were strongly correlated with BTK protein levels. BTK-High subtype showed increased CCL3/CCL4 levels and disease burden such as high WBC. BTK-Low subtype showed down-regulated mRNA/proteins of DNA-repair pathway and increased DNA-damage-response, which may have contributed to enrichment of inflammatory pathway. BTK-Low subtype was rich in proapoptotic gene and protein expression and relied less on BCR pathway. High-BTK subgroup was enriched in replication/repair pathway and transcription machinery. In conclusion, profiling of 5 datasets of ~700 patients revealed unique BTK-associated expression clusters in CLL.

Distinct chromosomal mutation associated with cefiderocol resistance in Acinetobacter baumannii: a combined bioinformatics and mass spectrometry approach to unveil and validate the in vivo-acquired chemoresistance

Acinetobacter baumannii is a significant public health concern due to the emergence of antibiotic-resistant strains. Cefiderocol (FDC), a novel siderophore cephalosporin, has shown promise as a last-line treatment for multidrug-resistant Gram-negative bacteria. However, the emergence of in vivo-acquired FDC-resistant A. baumannii strains highlights the need for advanced tools to identify resistance-associated genomic mutations and address the challenges of FDC susceptibility testing. This study aims to characterize a novel mutation responsible for FDC resistance in A. baumannii and to develop a workflow that integrates genomic and functional analyses for improved antimicrobial resistance monitoring. We examined two carbapenem-resistant A. baumannii isolates from bacteremia cases in two patients (A. baumannii_5406 from patient A and A. baumannii_5577 from patient B). Initial whole-genome sequence BLAST typing identified both as the same strain. However, a minimum inhibitory concentration (MIC) analysis showed that A. baumannii_5406 was resistant to FDC, while _5577 was not. Further variant calling analysis revealed a novel chromosomal mutation in a gene encoding a TonB-dependent receptor homolog, which is involved in ferric-siderophore and heme uptake. This mutation causes a premature stop codon, likely impairing the receptor’s function. Mass spectrometry confirmed that the FDC-resistant strain exhibited reduced antibiotic uptake and intracellular accumulation. This study demonstrates the utility of combining genomic and functional analyses to detect emerging mutations associated with antibiotic resistance. The variant calling approach, together with LC–MS/MS technology, offers a valuable complement to traditional susceptibility testing in clinical settings, potentially improving the identification and monitoring of FDC resistance in A. baumannii. Additionally, this workflow could aid in the epidemiological tracking of resistant strains.

The impact of high-risk cytogenetic abnormalities in extramedullary multiple myeloma in the era of novel agents: insights from a multicenter study

PurposeThis study aimed to examine the impact of high-risk cytogenetic abnormalities (HRA) on the survival outcomes of multiple myeloma patients with extramedullary disease (EMD) in the era of novel agents, utilizing the largest dataset of extramedullary multiple myeloma patients in China.MethodsThis study included a total of 371 patients with EMD, comprising 113 patients with de novo EME and 258 patients with EMB.ResultsPatients with one HRA and those with ≥ 2 HRA demonstrated significantly worse overall survival (OS) (P < 0.01) and progression-free survival (PFS) (P < 0.01) compared to patients without HRA. Additionally, 1q21 gain/amplification (1q21 +) remained a predictor of poor prognosis in EMD. CD38 monoclonal antibody-based therapy and single transplantation were less effective in improving survival outcomes for EMD with ≥ 2 HRA. Multivariable analysis identified LDH levels > 250 U/L, creatinine levels > 177 μmol/L, extramedullary extraosseous (EME), 1 HRA, and ≥ 2 HRA as independent adverse prognostic factors in patients with EMD.ConclusionPatients with EMD who had ≥ 2 HRA experienced an extremely poor prognosis, which could not be improved by single transplantation or CD38 monoclonal antibody-based treatment. The number of HRA could serve as an important factor in guiding treatment choices and predicting prognosis in patients with EMD. Furthermore, 1q21 + remained a significant factor associated with worse survival outcomes in EMD.

Prenatal diagnosis and molecular cytogenetic analysis of pure chromosome 10p15.3 microdeletion using chromosomal microarray analysis

BackgroundThe literature contains exceedingly limited reports on chromosome 10p15.3 microdeletions. In the present study, two cases of fetuses with pure terminal 10p15.3 microdeletion syndrome in a Chinese population were examined, with the objective of enhancing understanding of the genotype-phenotype correlation associated with 10p15.3 microdeletions.MethodsTwo fetuses with chromosome 10p15.3 microdeletion were identified from a cohort of 5,258 cases undergoing amniocentesis. Karyotyping and chromosomal microarray analysis (CMA) was conducted to assess chromosomal abnormalities and detect copy number variations (CNVs) within the families, respectively.ResultsIn Family 1, the fetus exhibited a 556.2-Kb deletion in the 10p15.3 region, encompassing OMIM genes such as DIP2C and ZMYND11, and presented with increased nuchal translucency on prenatal ultrasound examination. Parental CMA analysis revealed that the 10p15.3 microdeletion was inherited from the father, who displayed mild language impairment. In Family 2, a comparable 10p15.3 microdeletion was identified in a fetus presenting with asymmetric butterfly vertebrae at T10 and T12, along with mild scoliosis of the spine. Family 1 elected to terminate the pregnancy, while Family 2 chose to continue. At a follow-up conducted at one year and eight months, the child demonstrated delays in both speech and motor development.ConclusionThe present study is the first to report two cases of pure terminal chromosome 10p15.3 microdeletion syndrome in fetuses, offering valuable insights for the prenatal diagnosis of 10p15.3 microdeletion syndrome. Further, it is the first to describe mild clinical features, specifically limited to language impairment, in a patient with 10p15.3 microdeletion syndrome.

Immortalization of Mesenchymal Stem Cells for Application in Regenerative Medicine and Their Potential Risks of Tumorigenesis

Regenerative medicine utilizes stem cells to repair damaged tissues by replacing them with their differentiated cells and activating the body’s inherent regenerative abilities. Mesenchymal stem cells (MSCs) are adult stem cells that possess tissue repair and regenerative capabilities and immunomodulatory properties with a much lower risk of tumorigenicity, making them a focus of numerous clinical trials worldwide. MSCs primarily exert their therapeutic effects through paracrine effects via secreted factors, such as cytokines and exosomes. This has led to increasing interest in cell-free therapy, where only the conditioned medium (also called secretome) from MSC cultures is used for regenerative applications. However, MSCs face certain limitations, including cellular senescence, scarcity, donor heterogeneity, complexity, short survival post-implantation, and regulatory and ethics hurdles. To address these challenges, various types of immortalized MSCs (ImMSCs) capable of indefinite expansion have been developed. These cells offer significant promise and essential tools as a reliable source for both cell-based and cell-free therapies with the aim of translating them into practical medicine. However, the process of immortalization, often involving the transduction of immortalizing genes, poses potential risks of genetic instability and resultant malignant transformation. Cell-free therapy is particularly attractive, as it circumvents the risks of tumorigenicity and ethical concerns associated with live cell therapies. Rigorous safety tests, such as monitoring chromosomal abnormalities, are critical to ensure safety. Technologies like inducible or suicide genes may allow for the controlled proliferation of MSCs and induce apoptosis after their therapeutic task is completed. This review highlights recent advancements in the immortalization of MSCs and the associated risks of tumorigenesis.

Navigating the Spectrum of Double-İnlet Left Ventricle Presentations: Contemporary Retrospective Cohort Study.

We presented the experience of a tertiary care center for maternal and fetal diseases and assessed the findings fetuses with double-inlet left ventricle (DILV) regarding fetal echocardiography, prenatal course including fetal growth and death, and postnatal outcome. In this retrospective study, patients diagnosed with DILV via prenatal ultrasound in the maternal-fetal medicine department between 2015 and 2023 were included to evaluate important aspects of prenatal diagnosis and course, as well as postnatal management and outcome. There were 33 DILV cases prenatally diagnosed and postnatally confirmed. Genetic abnormality was detected in two (8%) of 25 fetuses that had undergone genetic tests. Pulmonary artery obstruction was observed in 10 (30.3%) fetuses; pulmonary stenosis was found in nine, and pulmonary atresia in one. Aortic arc abnormalities were found in 11 (33.3%) fetuses. The great arteries were malpositioned in the 29 (87.8%) fetuses. The median duration of follow-up for the infants was 12 (2-96) months, and 22 (66.6%) of 33 cases survived. Among the 27 (81.8%) live births, 24 infants required univentricular palliation. Remarkable implications of this study were that unless extra-cardiac and genetic anomalies accompany DILV, the probability of a chromosomal anomaly is low; that univentricular repair could be performed in almost all cases; and that the major causes of poor prognosis may be related to the restrictive bulboventricular foramen and severe aortic obstruction. Although long-term survival rates after univentricular repair appear to be high, these patients require long-term follow-up and repeated surgical procedures.

Conventional Cytogenetic Analysis of Solid Tumor Abnormalities: A 25-Year Review of Proficiency Test Results from the College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee

Background: The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure the competency and proficiency of clinical cytogenetic testing laboratories through proficiency testing (PT) programs for various clinical tests offered by such laboratories, including the evaluation of cytogenetic abnormalities in solid tumors. Methods: Review and analyze 25 years (1999–2023) of solid tumor chromosome analysis PT results, utilizing G-banded karyograms. A retrospective review of results from 1999 to 2023 was performed, identifying the challenges addressing solid tumors. The chromosomal abnormalities and overall performance were evaluated. Results: A total of 21 solid tumor challenges were administered during the period 1999–2018. No solid tumor challenges were administered during the period 2019–2023. Challenges consisted of metaphase images and accompanying clinical history for the evaluation of numerical and/or structural abnormalities. All 21 cases reached 80% grading consensus for abnormality recognition. However, five cases (24%) failed to reach consensus for nomenclature reporting by participating laboratories. These cases illustrate errors in reporting chromosomal abnormalities, including whole-arm translocations and those involving sex chromosomes. In addition, they highlight the challenges with differentiation of terminal and interstitial deletions, difficulties in identifying correct breakpoints, and omission of brackets in neoplastic cases. Conclusions: This comprehensive 25-year review demonstrates the exceptional proficiency of cytogenetic laboratories in accurately identifying chromosome abnormalities in solid tumors, while also highlighting the challenges of reporting specific types of chromosomal abnormalities.

A Narrative Review of Molecular, Immunohistochemical and In-Situ Techniques in Dermatopathology

Skin disorders pose a significant health burden globally, affecting millions of individuals across diverse demographics. Advancements in molecular techniques have revolutionised our understanding of the underlying mechanisms of skin disorders, offering insights into their pathogenesis, diagnosis, and potential targeted treatment. Furthermore, the integration of molecular diagnostics into clinical practice has enhanced the accuracy of skin disorder diagnoses. Polymerase chain reaction (PCR), next-generation sequencing (NGS), and other molecular assays have allowed for the detection of infectious agents, assessment of genetic mutations, and profile gene expression patterns with unequalled precision. These techniques have proven instrumental in distinguishing between subtypes of skin cancers, aiding treatment strategies and prognostic assessments. Moreover, molecular profiling is increasingly guiding the selection of therapeutic agents, ensuring a personalised and effective approach to managing skin disorders. The application of PCR has revolutionised the field by enabling the identification of microbial DNA (i.e., Mycobacterium tuberculosis and Epstein-Barr Virus) in skin infections and detecting specific genetic mutations associated with dermatological disorders (e.g., BRAF). DNA sequencing technologies, such as next-generation sequencing, have facilitated the elucidation of genetic variations and mutations in skin diseases (i.e., bullous disorders), paving the way for personalised treatment approaches. Gene expression profiling techniques, such as microarrays and RNA sequencing, have provided insights into dysregulated pathways and molecular signatures associated with conditions ranging from inflammatory skin disorders to cutaneous malignancies. Immunohistochemistry and fluorescence in situ hybridization have proven invaluable in determining protein expression patterns and detecting chromosomal abnormalities, respectively, aiding in the characterization of skin lesions in conjunction with the molecular data. Proteomic studies have contributed to understanding the intricate protein networks involved in dermatological conditions (i.e., psoriasis), while epigenetic analyses have shed light on the role of epigenetic modifications in gene regulation within skin cancer (i.e., Malignant Melanoma). Together, these molecular techniques have laid the groundwork for targeted therapies and precision medicine in dermatology, with implications for improved diagnostics and treatment outcomes. This review focuses on the routinely employed molecular techniques within dermatopathology, with a focus on cutaneous malignancies, autoimmune diseases, infectious diseases, and neonatal screening which can be implemented in the diagnosis and contribute to improved patient care.

Adverse Obstetric Outcomes in Pregnancies With Major Fetal Congenital Heart Defects.

Understanding the risk profile of obstetric complications in pregnancies with fetal major congenital heart defects (MCHDs) is crucial for obstetric counseling and care. To investigate the risk of placenta-related adverse obstetric outcomes in pregnancies complicated by fetal MCHDs. This cohort study retrieved data from June 1, 2008, to June 1, 2018, from the Danish Fetal Medicine Database, which includes comprehensive data on more than 95% of all pregnancies in Denmark since the database was instituted in 2008. All singleton pregnancies that resulted in a live-born child after 24 weeks' gestation without chromosomal aberrations were included. A systematic search of the literature was performed in PubMed, Embase, and the Cochrane Library from inception to June 1, 2024, to compile existing knowledge and data on adverse obstetric outcomes among MCHD subtypes. Fetal MCHDs including 1 of 11 subtypes. The primary outcome was a composite adverse obstetric outcome defined as preeclampsia, preterm birth, fetal growth restriction, or placental abruption. Secondary outcomes consisted of each adverse obstetric event. Adjusted odds ratios (AORs) were computed using generalized estimating equations adjusted for maternal body mass index, age, smoking, and year of delivery. Meta-analyses were conducted using random-effects models to pool effect sizes for each MCHD subtype and adverse obstetric outcome. A total of 534 170 pregnancies were included in the Danish cohort, including 745 with isolated fetal MCHDs (median [IQR] maternal age, 29.0 [26.0-33.0] years) and 533 425 without MCHDs (median [IQR] maternal age, 30.0 [26.0-33.0] years). Pregnancies with fetal MCHDs exhibited a higher rate of adverse obstetric outcomes at 22.8% compared with 9.0% in pregnancies without fetal MCHDs (AOR, 2.96; 95% CI, 2.49-3.53). Preeclampsia (AOR, 1.83; 95% CI, 1.33-2.51), preterm birth at less than 37 weeks (AOR, 3.84; 95% CI, 3.15-4.71), and fetal growth restriction (AOR, 3.25; 95% CI, 2.42-4.38) occurred significantly more frequently in pregnancies with MCHDs. Except for fetal transposition of the great arteries (AOR, 1.19; 95% CI, 0.66-2.15), all MCHD subtypes carried a greater risk of adverse obstetric outcomes. The meta-analysis included 10 additional studies that supported these results. These findings suggest that nearly 1 in 4 women expecting a child with an MCHD, except transposition of the great arteries, may be at high risk of adverse obstetric outcomes.

DeSUMOylating isopeptidase 1 participates in the faithful chromosome segregation and vincristine sensitivity.

SUMOylation, the modification of proteins with a small ubiquitin-like modifier (SUMO), is known to regulate various cellular events, including cell division. This process is dynamic, with its status depending on the balance between SUMOylation and deSUMOylation. While the regulation of cell division by sentrin-specific protease (SENP) family proteins through deSUMOylation has been investigated, the role of another deSUMOylase, deSUMOylating isopeptidase 1 (DESI1), remains unknown. In this study, we explored DESI1's role in cell division. Knockdown of DESI1 accelerated cell division progression, leading to a significant increase in abnormal chromosome segregation. These phenotypes were rescued by re-expression of wild-type DESI1, but not catalytically inactive DESI1. DESI1 knockdown reduced the mitotic arrest caused by nocodazole, suggesting DESI1's involvement in the spindle assembly checkpoint (SAC). Localization of Aurora B, a key SAC regulator, at the metaphase chromosomes was reduced due to decreased Aurora B expression upon DESI1 knockdown. Consistently, DESI1 knockdown reduced transcription of FoxM1 target genes, such as Aurora B, cyclin B1, and CENP-F. The TCGA database showed that both decreased and increased DESI1 expression levels are associated with poor prognosis in patients with certain cancer types. Importantly, we found that DESI1 knockdown reduced sensitivity to vincristine by inducing mitotic slippage. These results suggest that DESI1 is required for faithful chromosome segregation via regulating FoxM1 transcriptional activity and thereby SAC activity in an isopeptidase activity-dependent manner. Our findings identified DESI1 as a novel regulator of cell division and a factor affecting cancer chemotherapy.

New insights into the nature and classification of myelodysplastic neopmasm

The World Health Organization's (WHO) International Agency for Research on Cancer (IARC) released the fifth edition of the Classification of Tumors of the Hematopoietic and Lymphoid Tissues, renaming myelodysplastic syndrome (MDS) to myelodysplastic neoplasm (still abbreviated as MDS). This new classification integrates next-generation sequencing data to standardize the disease's nature. The name change reflects a deeper understanding of the disease, transitioning from the vague "syndrome" to a clearly defined neoplastic disease. The new classification divides MDS into two major categories: cytogenetic abnormalities and morphological abnormalities. Cytogenetic abnormalities include MDS with low blasts and isolated 5q deletion, MDS with low blasts and SF3B1 mutation, and MDS with biallelic TP53 alterations. Morphological abnormalities include MDS with low blasts, MDS with increased blasts and hypoplastic MDS. This revision provides a foundation for precise diagnosis and treatment of MDS, further restricting the application of immunosuppressive therapy and advancing genetic research in diagnostics and therapeutics.

Analysis of the clinical outcomes of fetal 6p22.1-p21.32 duplications signaled by non-invasive prenatal screening

To summarize the results of prenatal diagnosis and outcome of pregnancy of fetuses with a high risk for 6p22.1.1-p21.32 duplication signaled by non-invasive prenatal screening (NIPS). Clinical information, results of prenatal diagnosis and pregnancy for fetuses with a high risk for 6p22.1-p21.32 duplication were collected and analyzed. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethic No. 2018-YB-08). Forty three pregnant women with a high risk for 6p22.1-p21.32 duplication were identified by NIPS, among whom 30 had accepted invasive prenatal diagnosis, and 27 fetuses were verified to be false positive. Three fetuses were found to have other chromosomal abnormalities, among whom two were rated to be likely benign CNV and 1 was rated to be likely pathogenic. Follow up of the 43 pregnant women revealed that 35 fetuses were normal after birth, 1 pregnancy was terminated, and 7 were lost to follow up. For pregnant women with a high risk for 6p22.1-p21.32 duplication signaled by NIPS, genetic counselor need to inform them the high false positive rate and recommend invasive prenatal diagnosis and/or ultrasound examination in order to reduce the psychological and economic burdens.

Optical genome mapping technology and its applications in genetic disease diagnosis

Optical genome mapping (OGM) is an emerging technology for the detection of genetic diseases based on physical mapping, which can detect numerical chromosomal abnormalities, copy number variation (CNV) and structural variation (SV) on a genome-wide scale. In recent years, a number of studies have proved that OGM, as a new generation of cytogenomic technique, has higher resolution and stronger ability to discover genomic variants compared with conventional genetic techniques. This article has systematically reviewed the principles, characteristics, advantages and limitations of OGM technology, and its applications in the diagnosis of genetic disorders.

Corneal Endothelial Cell Morphology in Eyes With Down Syndrome.

To explore the morphological characteristics of corneal endothelial cells in eyes with Down syndrome. We conducted a comparative analysis of corneal endothelial cell density, coefficient of variation, hexagonal cell appearance rate, and corneal thickness using specular microscopy. Our study included 21 eyes of 11 patients with Down syndrome and 37 eyes of 19 control subjects. In all eyes with Down syndrome, corneal endothelial cell density exceeded 2000 cells/mm2, and no abnormalities in cell morphology or significant differences from the control group were observed across all parameters. The structure and function of corneal endothelial cells in eyes with Down syndrome were within the normal range, even in the presence of chromosomal abnormalities of 21-trisomy in somatic cells.

Research progress on the cognitive deficit of Down syndrome patients

As the most common chromosomal disorder compatible to life, Down syndrome (DS) is caused by an extra copy of chromosome 21. Almost all DS patients have cognitive dysfunction. Therefore, it is important to study the underlying pathogenetic mechanism to elucidate its molecular basis. This article has provided a review for the molecular mechanisms of NRIP1 and DYRK1A genes, which have been closely associated with the cognitive dysfunctions of DS patients. It has also summarized the research progress on the mechanism of DS and development of new therapeutic strategies based on such studies, with an aim to provide insights into the prevention and treatment for the cognitive dysfunctions in DS patients.

Genotype–Phenotype Correlation in a Couple in Which the Wife Is a Carrier of the Beta-Thalassemia Trait and the Husband Is a Carrier of a Mutation in the ALAS2 Gene: Both Gene Defects Are Associated with Non-Iron-Deficiency Microcytic Anemia

Introduction: Generally, microcytic anaemia is caused by sideropenia or a genetic gap. The suspicion that microcytic anaemia is caused by a genetic gap must always be considered in the face of an inadequate response to martial therapy. The aim of this paper is to highlight how biochemical diagnosis alone is sometimes not sufficient to understand the cause of microcytic anaemia. For this reason, for a correct genotype–phenotype correlation, it is essential to identify the defective gene underlying the microcytic anaemia. Detailed Case Description: This case concerns a married couple who both have microcytic anaemia. They came to our attention because the lady, pregnant at 12 weeks, underwent screening for chromosomal abnormalities using combined tests in the first trimester of pregnancy. A biochemical screening performed ten years earlier showed that both spouses were healthy carriers of the beta-thalassemia trait. A careful analysis of the biochemical data and an in-depth molecular diagnosis of the alpha and beta globin genes showed that the woman was a healthy carrier of the beta-thalassemia trait while the husband was a healthy carrier of a mutation in the ALAS2 gene. Analysis of the biochemical data of her husband and family members revealed that she had X-linked microcytic sideroblastic anaemia caused by an alteration in the function of the ALAS2 (5′-Aminolevulinate Synthase 2) gene located on the short arm of the X chromosome (Xp11.21). Discussion and Conclusions: This result is very relevant as, during genetic counselling, we explained to the couple that invasive prenatal diagnosis was not necessary as there is no risk of procreating a transfusion-dependent individual.

Accuracy of cell-free fetal DNA in detecting chromosomal anomalies in women experiencing miscarriage: systematic review and meta-analysis.

To report the diagnostic accuracy of cell-free fetal DNA (cfDNA) in detecting fetal chromosomal anomalies in women experiencing miscarriage. PubMed, MEDLINE, EMBASE and Cochrane databases were searched from inception to June 2024. The inclusion criteria were women experiencing miscarriage (defined as pregnancy loss before 20 weeks of gestation) who underwent cfDNA screening for trisomies 21, 18and13, other autosomal aneuploidies, sex-chromosome aneuploidies and/or copy-number variants (CNVs). The index test was cfDNA screening for each of the chromosomal anomalies listed. The reference standard was cytogenetic analysis of pregnancy tissue. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were computed using the hierarchical summary receiver-operating-characteristics model. Seven studies (887 women) were included in the systematic review and meta-analysis. cfDNA had a sensitivity and specificity of 100% (95% CI, 81.5-100%) and 100% (95% CI, 99.1-100%), respectively, for trisomy 21, 100% (95% CI, 54.1-100%) and 100% (95% CI, 99.0-100%), respectively, for trisomy 18, and 88.9% (95% CI, 51.8-99.7%) and 100% (95% CI, 99.1-100%), respectively, for trisomy 13. The respective values for other autosomal trisomies were 75.8% (95% CI, 65.7-84.2%) and 99.4% (95% CI, 97.9-99.9%), while those for CNVs were 60.0% (95% CI, 14.7-94.7%) and 100% (95% CI, 97.4-100%). Failure of cfDNA testing was reported in 7.3% (95% CI, 5.7-9.2%) of cases. cfDNA has high diagnostic accuracy in detecting fetal trisomies 21, 18 and 13 in women experiencing miscarriage, while its accuracy for other autosomal aneuploidies and CNVs is only moderate. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of chromosomal microarray and karyotyping in prenatal diagnosis using 491 amniotic fluid samples.

This study was aimed to investigate the performance of chromosomal microarray analysis (CMA) in prenatal diagnosis compared with traditional karyotyping analysis. Both CMA and karyotyping analyses were performed to detect the karyotypes in the amniotic fluid of 491 pregnant women who got prenatal diagnosis at the Center of Prenatal Diagnosis of Shangrao (China) during January 2019 to April 2021. After excluding 2 samples in the CMA analysis and 2 samples in the karyotyping analysis which were failed in detection, the remaining 487 amniotic fluid samples were detected. Both CMA and karyotyping analyses identified 22 cases of aneuploidy chromosome abnormalities, including trisomy 21 (10 cases), trisomy 18 (4 cases), sex chromosome abnormality (5 cases), and other chromosome abnormalities (3 cases). In addition, CMA and karyotyping analyses found 8 cases of fetal chromosomal imbalance. Interestingly, abnormal results were detected by CMA analysis in 10 cases whose results were normal by karyotype analysis. Furthermore, 23 cases of copy number variation (CNVs) with variation of unknown clinical significance (VOUS) were detected by CMA, which accounted for 4.68% (23/491) in all cases. However, CMA was not able to accurately identify some complex karyotypes and mixed chimeras, including 2 cases of chimeras, 4 cases of balanced translocations, 4 cases of pericentric inversions, and 8 cases of other chromosome polymorphisms, indicating karyotyping analysis was superior to detect these chromosome abnormalities compared with CMA analysis. CMA was better in detecting the fracture sites, microduplication and microdeletion with definite pathogenicity, and CNVs with VOUS compared with karyotype analysis.

Extra X, extra questions: Trisomy X syndrome and IgA deficiency – a case report

While Trisomy X syndrome is typically characterized by developmental and cognitive variations, it is not commonly associated with immunodeficiencies. We report the unique case of a 6-year-old girl with Trisomy X presenting with selective IgA deficiency, challenging the conventional understanding of this chromosomal condition. The patient exhibited recurrent respiratory infections and gastrointestinal symptoms, evaluated in the context of her genetic background of Trisomy X and significantly low levels of IgA (0.03 g/L), yet normal IgG and IgM levels. Immunological assessment revealed a poor response to vaccination to HBV, necessitating an adapted vaccination strategy. Gastrointestinal investigations indicated paradoxical diarrhea secondary to chronic constipation, managed with dietary interventions. The presence of an extra X chromosome raises questions about the potential over-expression of genes that escape X-chromosome inactivation, such as FOXP3, which is crucial for the regulation of regulatory T cells. An abnormal expression of FOXP3 could lead to either heightened immune regulation, increasing susceptibility to infections, or to immune dysregulation. Although Trisomy X is not typically associated with immunodeficiencies, this case, paralleled by another patient with Trisomy X and CVID, suggests a need for further speculative research into possible genetic links. Moreover, a 1969 study reported lower IgA levels in women with an extra X chromosome. In conclusion, this case aims to underscore the necessity for a deeper genetic and immunological evaluation in chromosomal anomalies like Trisomy X to fully understand their speculative impact on immune function.