Chromosomal Microarray Research Articles

Diagnostic Accuracy and Chromosomal Microarray and Karyotype Analysis with Different Clinical Biomarkers for Prenatal Diagnosis of Fetal Genetic Diseases

Background: We compared the diagnostic accuracy and application value of chromosome microarray (CMA) technique and karyotype analysis for prenatal diagnosis of fetal genetic diseases using different clinical markers. Methods: This is a prospective clinical study involving 1587 pregnant women who underwent amniocentesis for prenatal diagnosis due to various abnormal clinical indications in China between May 2018 and Nov 2021. Both chromosome microarray and karyotype analysis were applied. Participants were categorized into six groups based on different indications for prenatal diagnosis. The detection rates of chromosome microarray and karyotype analysis were compared. The study utilized SPSS version 20 for data analysis, employing descriptive statistics for count data results and chi-square statistics for statistical associations between outcomes and predictors. Results: Chromosome microarray and karyotype analysis detected more abnormal chromosomes in the group with abnormal NIPT, with positive detection rates of 59.68% and the group in other situation with positive detection rates of 39.22%. Overall, 343 chromosome abnormalities were detected among participants. Overall, 101 cases chose induced labor, 240 cases gave birth, 1 newborn died after delivery, 1 case of twin chose selective reduction, another fetus gave birth, and 1 case lost to follow-up. The detection rate of chromosome abnormality in high-risk population was more than 1/5, highlighting the importance of reducing the incidence of birth defects through interventional prenatal diagnosis. Conclusion: Clinically, Down's screening, NIPT and prenatal ultrasound screening can be conducted initially, followed by karyotype analysis and CMA detection for those with abnormal findings.

Diagnostic Yield of Chromosomal Microarray Analysis in a Cohort of 300 Indian Patients.

To present authors' experience of chromosome microarray analysis (CMA) as the first-tier test, which contributed to accumulation and annotation of copy number variations (CNVs) and discovery of novel genetic hot spots in Indian pediatric patients. Karyotyping and CMA (4X180K Agilent) were performed in 300 patients with developmental delay, dysmorphism, autism, intellectual disability or congenital malformations. Various databases such as ClinVar, Clin Gen, OMIM, DECIPHER, etc. were used for interpretation of the results. The diagnostic yield of clinically significant findings by CMA [16.00% (48/300)] was 9.0% higher than that by karyotyping [7.0% (21/300)]. There were 2.66% (08/300) patients with variations of uncertain significance (VOUS) which were challenging to interpret. Benign variations were considered normal. CMA allows increased diagnostic yield of known and new microdeletion/duplication syndromes and molecular characterization of marker chromosomes with gene annotations. There is insufficient data published from India. Every such test done on Indian patients contributes to Indian data accumulation of pathogenic CNVs (pCNVs) and VOUS for future resolution. The benefit of CMA as a first-tier test is that it can improve the understanding towards the associated known and new genetic hot spots, thus providing a better genotype-phenotype correlation. Pre-test and post-test genetic counseling is important.

Clinical features and genetic analysis of a family with t(5;9) (p15;p24) balanced translocation leading to Cri-du-chat syndrome in offspring

BackgroundBalanced translocations are common chromosomal structural abnormalities that usually do not involve a gain or loss of genetic material; and carriers usually display normal phenotypes and intelligence. However, unbalanced rearranged gametes can be produced during the meiotic division of reproductive cells, leading to infertility, miscarriage, stillbirth, or the birth of newborns with malformations and chromosomal abnormalities. These adverse pregnancy outcomes create significant burdens for families and societies and affect the quality of life of newborns, threatening their health.ObjectiveIndividuals carrying balanced translocations can have phenotypically normal offspring, but they also face high risks of natural miscarriage and giving birth to newborns with chromosomal abnormalities. We characterized individual clinical features and conducted a genetic analysis of the members of a family with t (5; 9) (p15; p24) balanced translocation leading to Cri-du-chat syndrome in the offspring.Study designWe performed a chromosomal karyotyping with high-resolution G-banding on the proband and her family members to detect their chromosomal configurations. We also used chromosomal microarray analyses (CMA) to detect copy number variants. Enrichment analysis of genes in the duplicated or deleted regions of 5p and 9p was performed using Metascape. Results: The proband (III7), her father (II3), her brother (III5), and her cousin (III14) were all carriers of the t (5; 9) (p15; p24) balanced translocation. Offspring (IV5, IV7, IV9, and IV12) were affected. Genetic microarray results of IV7 showed a 26.3 Mb deletion on chromosome five and a 15.3 Mb duplication on chromosome 9. Genetic microarray results of IV5, IV9, and IV12 showed a 26.5 Mb duplication on chromosome five and a 15.4 Mb deletion on chromosome 9.ConclusionThis study reports a rare familial balanced translocation pedigree, particularly noting that the offspring can suffer from Cri-du-chat syndrome, which suggests a potential new genetic model for this syndrome. It provides novel insights for genetic counseling and prenatal diagnosis in patients with adverse pregnancy outcomes before attempting another pregnancy.

Reporting Criteria for Prenatally Identified Variants of Uncertain Significance Differs Among Cytogenetics Laboratories in North America.

Current technical standards for chromosomal microarray (CMA) interpretation are not prescriptive for reporting variants of uncertain significance (VUS) identified prenatally. We sought to compare prenatal CMA reporting among cytogenetic labs and identify potential drivers of practice variation. We conducted an electronic cross-sectional survey of cytogeneticists in the United States and Canada from July-December 2023. Participants were identified through the American Cytogenetics Forum List. Labs reported differences in their size threshold used when reporting CNVs lacking OMIM annotated genes as a VUS, variable use of clinical data such as ultrasound or family history when deciding to report a VUS, and differences in opinion regarding the underlying pathogenicity of certain CNVs. Many cytogeneticists reported concerns about legal liability related to prenatal CMA reporting, and many shared concerns that a patient may terminate a pregnancy based on a VUS. Reporting criteria for prenatally identified variants of uncertain significance differs among cytogenetic laboratories in North America. Many possible drivers of this practice variation were identified, including a lack of national guidelines that comprehensively address the unique considerations for prenatal CMA reporting.

Crop-specific Biotic Stress Management: Leveraging Cytogenetic Insights

Biotic stresses pose significant challenges to global crop production, threatening food security and agricultural sustainability. Effective management of biotic stressors, including pathogens, pests, and weeds, is essential to mitigate yield losses and ensure crop productivity. Cytogenetics, a branch of genetics focusing on the study of chromosomes and their inheritance patterns, offers valuable insights and tools for understanding the genetic basis of biotic stress resistance in crops. In this review, we provide an overview of the applications of cytogenetics in biotic stress management, highlighting its role in elucidating genetic mechanisms of resistance, identifying molecular markers for breeding programs, and enhancing crop resilience to biotic stressors. For instance, drought tolerance mechanisms differ in wheat (Triticum aestivum) and rice (Oryza sativa), with wheat exhibiting higher osmotic adjustment through proline accumulation, whereas rice relies more on root plasticity and antioxidant enzyme activity. Similarly, heat stress responses in maize (Zea mays) and soybean (Glycine max) highlight the role of heat shock proteins and photosynthetic efficiency under high-temperature conditions. By integrating cytogenetic techniques and methodologies used in cytogenetic analysis, including karyotyping, fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), fluorescence-activated cell sorting (FACS), polymerase chain reaction (PCR), chromosome banding techniques, microarray analysis, and next-generation sequencing (NGS) we can overcome this biotic stresses too. This review also addresses the challenges and limitations of cytogenetic approaches and discusses future research directions. By synthesizing advancements in cytogenetics and stress management, this article serves as a comprehensive resource for researchers, plant breeders, and agricultural stakeholders focused on sustainable crop production.

Prenatal Diagnosis and Clinical Phenotypic Heterogeneity of 22q11.2 Microdeletion Syndrome Based on a Single Center Retrospective Study.

To retrospectively investigate the incidence of prenatal diagnosis of 22q11.2 microdeletion syndrome (22q11.2DS) in a single center and summarize its clinical manifestations to expand the phenotypic database. Pregnant women who underwent prenatal diagnosis at The Women and Children's Hospital, School of Medicine, Xiamen University, from January 2018 to February 2024 were retrospectively analyzed. Prenatal diagnosis was performed using routine G-banding karyotype analysis and chromosomal microarray analysis (CMA) or copy number variation sequencing (CNV-seq). Fetuses diagnosed with 22q11.2DS were further analyzed using detailed ultrasound diagnostic records to summarize the clinical manifestations of 22q11.2DS. A total of 24,319 pregnant women underwent prenatal diagnosis, and 24 cases were diagnosed with 22q11.2DS, with an incidence of 0.99‰ (24/24319), including 16 cases of congenital heart disease, 4 cases of renal pelvis separation, 3 cases of cleft lip and palate, 2 cases of double strephenopodia, 2 cases of nasal bone dysplasia, and 1 case each of unclear thymus, spina bifida with meningomyelocele, abnormal fetal growth retardation, and NT thickening. Congenital heart disease was the most common phenotype in 22q11.2DS, and other malformations also occurred in a certain proportion. In addition, some rare clinical phenotypes, such as spina bifida with myelomeningocele and nasal bone hypoplasia, were also found in this cohort, which should be taken seriously to improve the detection rate of fetal 22q11.2DS.

Optical genome mapping improves clinical interpretation of constitutional copy number gains and reduces their VUS burden.

Optical genome mapping improves clinical interpretation of constitutional copy number gains and reduces their VUS burden.

Mosaic STS gene deletions in chorionic villus samples are often confined to the placenta, and they differ in size from STS gene deletions in patients with X-linked Ichthyosis.

Mosaic STS gene deletions in chorionic villus samples are often confined to the placenta, and they differ in size from STS gene deletions in patients with X-linked Ichthyosis.

A Droplet Digital Polymerase Chain Reaction-Based Tool to Aid in Melanoma Diagnosis: Development of a 4-Gene Panel Using 164 Melanocytic Neoplasms.

Detecting copy number variations (CNVs) at certain loci can aid in the diagnosis of histologically ambiguous melanocytic neoplasms. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and inexpensive method for CNV detection in other cancers, but not yet melanoma. To evaluate the performance of a 4-gene ddPCR panel that simultaneously tests for ras responsive binding element protein 1 (RREB1) gain; cyclin-dependent kinase inhibitor 2A (CDKN2A) loss; MYC proto-oncogene, bHLH transcription factor (MYC) gain; and MYB proto-oncogene, transcription factor (MYB) loss in melanocytic neoplasms. One hundred sixty-four formalin-fixed, paraffin-embedded skin samples were used to develop the assay, of which 65 were used to evaluate its performance. Chromosomal microarray analysis (CMA) data were used as the gold standard. ddPCR demonstrated high concordance with CMA in detecting RREB1 gain (sensitivity, 86.7%; specificity, 88.9%), CDKN2A loss (sensitivity, 80%; specificity, 100%), MYC gain (sensitivity, 70%; specificity, 100%), and MYB loss (sensitivity, 71.4%; specificity, 100%). When one CNV was required to designate the test as positive, the 4-gene ddPCR panel distinguished nevi from melanomas with a sensitivity of 78.4% and a specificity of 71.4%. For reference, CMA had a sensitivity of 86.2% and a specificity of 78.6%. Our data also revealed interesting relationships with histology, namely (1) a positive correlation between RREB1 ddPCR copy number and degree of tumor progression; (2) a statistically significant correlation between MYC gain and nodular growth; and (3) a statistically significant correlation between MYB loss and a sheetlike pattern of growth. With further validation, ddPCR may aid both in our understanding of melanomagenesis and in the diagnosis of challenging melanocytic neoplasms.

A Novel Frameshift Variant and a Partial EHMT1 Microdeletion in Kleefstra Syndrome 1 Patients Resulting in Variable Phenotypic Severity and Literature Review

Background: Kleefstra syndrome 1(KLEFS1, OMIM#610253) is a rare neurodevelopmental disorder (NDD) instigated by heterozygous variants or microdeletions occurring in the 9q34.4 genomic region of the euchromatic histone methyltransferase-1 (EHMT1) gene and is inherited in an autosomal dominant (AD) manner. The clinical phenotype of KLEFS1 includes moderate to severe intellectual disability (ID), hypotonia, and distinctive facial features and additionally involves other organ systems (heart, renal, genitourinary, sensory) albeit with phenotypic heterogeneity between patients. The purpose of this study is to expand the genotypic spectrum of KLEFS1 and compare phenotypic features of the syndrome of already published cases. Methods: Exome sequencing (ES), chromosomal microarray analysis (CMA), as well as sanger sequencing, for confirmation of the de novo status of the frameshift variant, were used. Results: Here we describe two more cases, both males with a similar age and carriers of novel variants; one with a frameshift variant involving exon 13: p.Val692Glyfs*64 and the other with the smallest so far described, 11 Kb (exons 19-25), 9q34.4 microdeletion: 9q34.3 (140703393-140714454). Both presented with an NDD disorder with one showing more severe ID with significant social disabilities, while the other with the microdeletion had mild ID and following a normal education curriculum. Neither of them were obese nor had any other significant organ system disorder. Conclusions: The observed phenotypic variability due to genotypic differences in the two children contributes to the expanding spectrum of KLEFS1 disease phenotypes.

Chromosomal Microarray Analysis in Spina Bifida: Genetic Heterogeneity and Its Clinical Implications

ABSTRACT Background: The etiology of spina bifida is multifactorial; the phenotype is the end result of both genetic and environmental influences. While whole exome sequencing has identified several pathogenic variants in Indian cohorts, the role of chromosomal imbalances and long contiguous stretches of homozygosity (LCSHs) remains largely unexplored in this population. Chromosomal microarray analysis (CMA) is an important tool that provides insights into such genetic aberrations, making it significant for evaluating patients with spina bifida. Objective: To identify LCSHs and chromosomal imbalances in three spina bifida patients through CMA analysis as a pilot investigation. Materials and Methods: Genomic DNA was isolated from three spina bifida patients (P1: 10-year-old female, P2: 1-year-old male, and P3: 2.8-year-old male) and subjected to CMA using the Affymetrix 750K high-density array platform. The submicroscopic chromosomal imbalances and LCSHs were cross-referenced with public databases (Database of Genomic Variants, ClinVar, and OMIM) to evaluate their clinical significance. Functional annotations of the affected genes were performed to understand their role in neural tube development. Results: CMA revealed significant LCSH on chromosomes 2, 3, and 7 involving the genes SOX11, WNT7A, FZD9, SEMA3A, and VHL, all of which are involved in neural tube closure. Mosaic Klinefelter syndrome (25.9% mosaicism) was identified in the second patient while the third patient had a normal genetic profile. The detection of significant genetic variations in two of three cases underscores the potential utility of CMA in spina bifida patients. Conclusions: This study has generated valuable insights into the complex genetic landscape underlying the multifactorial etiopathogenesis of spina bifida. The findings not only underscore the importance of an integrated approach but also support the cause of a platform for large-scale investigations in the Indian population.

Exploring copy number variations in Lebanese families with rod-cone dystrophy reveals a novel deletion in PRPF31 with haploinsufficiency

ABSTRACT Background and Objectives Rod-cone dystrophy (RCD), also known as retinitis pigmentosa, is the most common group of retinal dystrophies, affecting around 1:4,000 individuals worldwide. In the present work, we performed a copy number variation (CNV) analysis on next-generation sequencing (NGS) data from two Lebanese families with RCD, since no disease-causing mutations were identified through the analysis of single nucleotide variants (SNVs) and insertions/deletions (Indels). NGS, real-time PCR (qPCR), and chromosomal microarray were performed to identify, validate, and delineate the causative CNVs identified in both families involved in this study. Additionally, expression analysis using qPCR and western blotting was conducted to assess the effect of the PRPF31 variant on gene and protein expression levels. Results A novel heterozygous deletion (701 bp) spanning exons 6 and 7 of PRPF31 was identified in the first family (F11), resulting in autosomal dominant RCD due to haploinsufficiency. This was confirmed by reduced mRNA levels and the complete absence of protein expression in the affected individuals (F11:III.2 and F11:II.2). In the second family (F26), we identified a previously documented homozygous deletion in the exons 3–19 of MERTK gene, which is responsible for causing severe autosomal recessive RCD. Conclusion The current study expands the mutational spectrum of PRPF31 and MERTK genes, underscoring the importance of CNVs and haploinsufficiency in RCD etiology. These findings serve as a foundation for future analyses concerning gene augmentation therapies.

Evaluation of Genomic Proximity Mapping (GPM) for Detecting Genomic and Chromosomal Structural Variants in Constitutional Disorders.

Genomic structural variants (SVs) are critical contributors to genetic diversity and disease, yet their detection remains challenging with conventional cytogenetic techniques, such as karyotyping, fluorescence in situ hybridization (FISH), and chromosome microarray analysis (CMA). These methods often lack the resolution and sensitivity needed for comprehensive characterization of chromosomal aberrations. To address these limitations, we implemented genomic proximity mapping (GPM), a genome-wide chromosome conformation capture technology, in a clinical setting. In this study, we applied GPM to a cohort of 123 patients with constitutional disorders, achieving a 100% concordance rate in detecting 411 CNVs and 39 structural rearrangements, in addition to novel findings missed by standard methods. GPM demonstrated unique advantages, such as resolving both balanced and unbalanced chromosomal rearrangements with precise (<5kb) breakpoint resolution, maintaining robust performance with challenging samples, including formalin-fixed, paraffin-embedded (FFPE) tissues, and detecting mosaicism with high sensitivity. Furthermore, GPM reliably provided detailed copy number and loss-of-heterozygosity profiles, streamlining workflows and enhancing diagnostic resolution. GPM represents a transformative tool for genomic diagnostics, offering a high-resolution, comprehensive approach to detecting diverse genomic alterations. Its ability to address limitations of conventional cytogenetics methods positions GPM as a needed advance in the diagnosis, prognosis, and therapeutic management of genetic disorders.

Application of Chromosomal Karyotype Analysis Combined With Chromosomal Microarray Analysis in the Amniotic Fluid of Advanced Maternal Age.

To explore the application and value of chromosomal karyotype analysis combined with Chromosomal Microarray Analysis (CMA) in the amniotic fluid of advanced maternal age. A total of 817 advanced maternal age (AMA) who underwent amniocentesis at the Prenatal Diagnosis Center of Huizhou Central People's Hospital between January 2018 and July 2024 were enrolled in this study. The women were grouped based on different age ranges and prenatal diagnosis factors. These groups were used to compare the detection rates and differences between chromosomal karyotype analysis and CMA. The overall chromosomal abnormality rates detected by karyotype analysis in the 35-39 years age group and the ≥ 40 years age group were 8.81% and 13.79%, respectively, with a statistically significant difference (p < 0.05). For CMA, the overall abnormality rates in the same age groups were 10.79% and 15.33%, respectively, but the difference was not statistically significant (p > 0.05). The non-solely advanced-age group (those with additional factors beyond just advanced age) had higher overall chromosomal abnormality rates, aneuploidy rates, structural abnormality rates, and mosaicism rates compared to the solely advanced-age group, with statistically significant differences (p < 0.05). Additionally, the non-solely advanced-age group had a higher overall abnormality rate detected by CMA compared to the solely advanced-age group, with a statistically significant difference (p < 0.05). However, there were no statistically significant differences between the two groups in terms of the detection of pathogenic, likely pathogenic, and variants of uncertain significance (p > 0.05). In this study, a total of 68 cases were identified where the results of karyotype analysis and CMA were inconsistent. The overall abnormal rate of chromosomal karyotype analysis increases with maternal age, while the overall abnormal rate of CMA shows no significant correlation with maternal age. The abnormal rates are significantly higher in AMA with additional factors. The combination of chromosomal karyotype analysis and CMA can validate and complement each other, thereby improving the detection rates of chromosomal abnormalities in amniotic fluid samples of AMA. This provides a diagnostic basis for subsequent pregnancy choices, which effectively reduces the birth of fetuses with chromosomal abnormalities and enhances population quality.

Clinical profile and cytogenetics of siblings with Jacobsen syndrome

Abstract The clinical care of patients has greatly benefited from the advancement of genetic testing. Over time, a gradual move toward a “genotype-first” strategy and growing use of genome-wide testing techniques such as chromosomal microarray analysis and next-generation sequencing have been noted to facilitate arriving at the diagnosis. However, the cost of these genetic tests is too high which people from low socioeconomic status cannot afford. Our case report was about one such affected family, in which both siblings were diagnosed with Jacobsen syndrome. We describe about a 2-year-old male child who has dysmorphic facial features, cardiac and renal defects, and developmental delay without thrombocytopenia. Segmental duplication (22.2 Mb) on the long arm of chromosome 14 and deletion of 5.9 Mb on 11q24 were revealed by chromosomal microarray analysis.

Efficiency of Chromosome Microarray Analysis Combined with Karyotyping in Fetuses with Abnormal Down Syndrome Screening Results

Objective: We aimed to explore the value of chromosome microarray analysis (CMA) and karyotyping in fetuses with a high risk for Down syndrome (DS) by serological screening and prenatal cell-free DNA(cfDNA) screening in Southwest China. Methods: We performed CMA and karyotype in 3028 pregnant women at high risk of DS. Results: Among 2,830 individuals identified as high-risk through serological screening for DS, 280 (9.89%) returned positive results. Subsequent karyotyping confirmed 51 cases of DS, 13 cases of sex chromosome aneuploidy, and 11 cases of trisomy 18. Moreover, CMA revealed 45 cases of pathogenic/likely pathogenic copy number ­variations (p/lpCNVs), 128 cases of uncertain significance(VOUS), and 32 cases of regions of homozygosity(ROH), with a 13.04% (205/280) increase in CMA yield compared to the karyotype analysis. Among 227 who had a high risk of prenatal cfDNA screening for DS, 181 (79.74%) exhibited positive results, including 179 cases with DS. Conclusion: Serological screening cannot be replaced by prenatal cfDNA screening. CMA, combined with karyotyping, has a high diagnostic value for DS and should be promoted.

Prenatal diagnosis of imprinted associated chromosome abnormalities identified by noninvasive prenatal testing (NIPT)

To explore the clinical value of noninvasive prenatal testing (NIPT) combined with chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV-seq), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), and fluorescence in situ hybridization (FISH) in the early screening of imprinted chromosome abnormalities. We retrospectively studied the prenatal diagnosis and pregnancy outcomes of 9 pregnant women with imprinted associated chromosome abnormalities via NIPT. All pregnant women received detailed genetic counselling and prenatal diagnosis. Karyotyping analysis, CNV-seq, CMA, FISH or MS-MLPA were performed on the amniotic fluid samples. We collected the intrauterine phenotypes via ultrasound and followed them up until the induction of labor or one year after birth. Six fetuses (6 out of 9) were diagnosed with regional abnormalities of Imprinting Disease. The most commonly diagnosed syndrome was 15q11-q13 duplication syndrome ( 3 out of 6), followed by mosaic trisomy 7 (2 out of 6) and Temple syndrome (1 out of 6). The other three fetuses (3 out of 9) were diagnosed with absence of heterozygosity (AOH). After genetic counselling, 4 pregnant women (4 out of 9) chose induced labor, 3 pregnant women (3 out of 9) chose spontaneous labor, and 2 pregnant women (2 out of 9) chose cesarean section. The widespread use of NIPT in prenatal screening provides more opportunities to detect rare chromosome aneuploidies (RCAs) and microdeletion/microduplication syndromes (MMSs) in mid-pregnancy. The combination of NIPT and other prenatal diagnostic technologies can help increase the possibility of detecting imprinting-related diseases with no phenotype or a late phenotype in utero.

Effective detection of 148 cases chromosomal mosaicism by karyotyping, chromosomal microarray analysis and QF-PCR in 32,967 prenatal diagnoses

BackgroundDetection of mosaicism has always been difficult in prenatal diagnosis, which is to assess the value of karyotyping combined with three different molecular genetic tests for prenatal diagnosis. Retrospective review of chromosomal mosaicism (CM) was conducted in 32,967 pregnant women from January 2015 to December 2022.MethodsA total of 148 fetuses diagnosed with chromosomal mosaicism by karyotyping with copy number variant sequencing (CNV-seq)/ chromosomal microarray analysis (CMA) and quantitative fluorescent polymerase chain reaction (QF-PCR) were selected, and the results from three the methods were compared and further analyzed. The χ2 test for multiple group rates was for the 5 clinical prenatal diagnostic indication groups was used to do multiple comparison tests for statistical analysis. Inconsistent results between methods were identified and further analyzed.ResultsA total of 148 CM cases was detected (0.45%, 148/32967), of which karyotyping was detected in combination with CMA in 73 cases (73/85), with CNV-seq in 5 cases (5/11), and with QF-PCR in 35 cases (35/52) and the mosaic conformity rates of the three methods compared with karyotyping were 85.9% (CMA), 67.3% (QF-PCR), and 45.5% (CNV-seq), respectively. There were 49 cases of autosomal mosaicism (49/148, 33.1%) and 99 cases of sex CM (99/148, 66.9%). There were 9 cases of small supernumerary marker chromosome (sSMC)with CMA detection clarified the origin of chromosome fragments. The non-invasive prenatal testing (NIPT) group and the ultrasound abnormality group had the highest detection rates, accounting for 35.1% and 22.3%.ConclusionsIn chromosomal mosaicism, there are inconsistent results between different detection methods. Therefore, karyotyping combined with CMA/CNV-seq and FISH methods significantly improves the detection rate of chromosomal mosaicism and also confirms experimental data in the literature, which is of great value for prenatal diagnosis.

Cytogenomic characterization of karyotypes with additional autosomal material

Chromosomal rearrangements involving additional material in individuals with phenotypic alterations usually result in partial trisomy, often accompanied by partial monosomy. To characterize chromosomal rearrangements and analyze genomic characteristics in the breakpoint regions in 31 patients with additional material on an autosomal chromosome. Different tests were performed to characterize these patients, including karyotyping, chromosomal microarray analysis (CMA), and fluorescent in situ hybridization (FISH). In silico analyses evaluated A/B chromosomal compartments, segmental duplications, and repetitive elements at breakpoints. The 31 rearrangements resulted in 47 copy number variations (CNVs) and a range of structural aberrations were identified, including six tandem duplications, 19 derivative chromosomes, two intrachromosomal rearrangements, one recombinant, two dicentric chromosomes, and one triplication. A deleted segment was associated with the duplication in 16 of the 19 patients with derivative chromosomes from translocation. Among the trios whose chromosome rearrangement origin could be investigated, 54,5% were de novo, 31,9% were maternally inherited, and 13,6% were paternally inherited from balanced translocations or inversion. Breakpoint analysis revealed that 22 were in the A compartment (euchromatin), 25 were in the B compartment (heterochromatin), and five were in an undefined compartment. Additionally, 14 patients had breakpoints in regions of segmental duplications and repeat elements. Our study found that a deletion accompanied by additional genetic material was present in 51.6% of the patients, uncovering the underlying genetic imbalances. Statistical analyses revealed a positive correlation between chromosome size and the occurrence of CNVs in the rearrangements. Furthermore, no preference was observed for breakpoints occurring in compartments A and B, repetitive elements, or segmental duplications.

Identifying a unique chromosomal pattern to predict the gemcitabine response in patients with cholangiocarcinoma

Cholangiocarcinoma (CCA) is an epithelial bile duct cancer frequently found at an advanced stage, leading to poor response to current therapies. Although gemcitabine (GEM) and cisplatin (CIS) are the current gold-standard for treating unresectable CCA, GEM resistance often occurs. To predict the response to GEM, we evaluated chromosomal aberrations using a chromosome microarray, and their association with GEM response by histoculture drug response assay. Our findings revealed principal component analysis and orthogonal partial-least square discriminant analysis cross validated score plot between response and non-response groups were different. Different signature patterns of chromosomes between response and non-response groups analyzed by heatmap analysis identified 34 regions of 15 chromosomes. An increased signal in responders and a decreased signal in non-responders were found in regions 4q32.1, 5q12.3, 10q21.3, 11p11.2, 11q14.2, 16p11.2, 17q22, 21q21.3 and 22q12.3. In contrast, a high signal in non-responders and low signal in responders were seen in regions 2q37.2, 11q14.1, 16q22.3 and 16q23.3. High signal of CDH13 and TENM4 were demonstrated in GEM non-response, while a high CWC27 signal was noted in GEM response. This signature pattern could provide the knowledge to improve a predictive biomarker for GEM response, benefitting for individual CCA patient management and chemotherapeutic selection.