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Objective: Copy number variations (CNVs) detected by high-resolution single nucleotide polymorphism microarrays (SNP arrays) have been associated with congenital heart defects (CHDs). The genetic mechanism underlying the development of CHDs remains unclear. Methods: High-resolution SNP arrays were used to detect CNVs and traditional chromosomal analyses, respectively, were carried out on 60 and 249 fetuses from gestational 12–37 weeks old, having isolated or complex CHDs that were diagnosed using prenatal ultrasound. Results: Twenty of the 60 fetuses (33.5%) had abnormalities, of which 23 CNVs (12 pathogenic, five probable pathogenic and six of undetermined significance) were detected by SNP arrays, and two distinct CNVs were present in three of these fetuses. In addition, in 39 patients with isolated congenital heart disease who had normal karyotypes, abnormal CNVs were present in 28.2% (11/39), and in patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. In patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. Conclusions: In conclusion, genome-wide high-resolution SNP array can improve the diagnostic rate and uncover additional pathogenic CNVs. The submicroscopic deletions and duplications of Online Mendelian Inheritance in Man (OMIM) genes found in this study have haploinsufficient (deletion) or triplosensitive (duplication) traits, which further clarify the etiology and inheritance of CHDs. [ABSTRACT FROM AUTHOR]

Abstract Background Chromosomal microarray analysis (CMA) has emerged as a critical instrument in prenatal diagnostic procedures, notably in assessing congenital heart diseases (CHD). Nonetheless, current research focuses solely on CHD, overlooking the necessity for thorough comparative investigations encompassing fetuses with varied structural abnormalities or those without apparent structural anomalies. Objective This study sought to assess the relation of single nucleotide polymorphism-based chromosomal microarray analysis (SNP-based CMA) in identifying the underlying causes of fetal cardiac ultrasound abnormalities. Methods A total of 2092 pregnant women who underwent prenatal diagnosis from 2017 to 2022 were included in the study and divided into four groups based on the presence of ultrasound structural abnormalities and the specific type of abnormality. The results of the SNP-Array test conducted on amniotic fluid samples from these groups were analyzed. Results Findings from the study revealed that the non-isolated CHD group exhibited the highest incidence of aneuploidy, overall chromosomal abnormalities, and trisomy 18, demonstrating statistically significant differences from the other groups (p 0.05). The occurrence rates of 22q11.2 and 15q11.2 were also not statistically different between the isolated CHD group and the non-isolated congenital heart defect group (p > 0.05). Conclusion SNP-based CMA enhances the capacity to detect abnormal CNVs in CHD fetuses, offering valuable insights for diagnosing chromosomal etiology and facilitating genetic counseling. This research contributes to the broader understanding of the utility of SNP-based CMA in the context of fetal cardiac ultrasound abnormalities.

(1) Background: At diagnosis, multiplemyeloma risk estimation includes disease burden, end-organ damage, and biomarkers, with increasing emphasis on genetic abnormalities. Multicolor flow cytometry (MFC) is not always considered in risk estimation. We demonstrate associations found between genetic abnormalities and antigen expression of plasma cells measured by MFC. (2) Methods: Single nucleotide polymorphism microarray (SNP-A) karyotyping as well as MFC using standardized next-generation flow (NGF) panels and instrument settings were performed from bone marrow aspirates at the time of diagnosis. (3) Results: We uncovered specific immunophenotype features related to different genetic risk factors. Specifically, we found higher malignant/normal plasma cell ratio and lower expression of CD27, CD38, CD45, CD56, CD117 and CD138 in higher-risk genetic groups or risk categories. [ABSTRACT FROM AUTHOR]

Xiaorui Xie, Xiaoqing Wu, Linjuan Su, Meiying Cai, Ying Li, Hailong Huang, Liangpu Xu Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Liangpu XuMedical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of ChinaTel +86 59187554929Email xiliangpu@fjmu.edu.cnBackground: The current gold standard of karyotype analysis for prenatal diagnosis of fetuses with central nervous system (CNS) abnormalities has some limitations. Here, we assessed the value of single nucleotide polymorphism (SNP) arrays as a diagnostic tool.Methods: The results of prenatal diagnosis of 344 fetuses with CNS abnormalities as determined by ultrasonographic screening were retrospectively analyzed. All fetuses underwent chromosomal karyotype analysis and genome-wide SNP array analysis simultaneously. The resultant rates and frequencies of genomic abnormalities were compared.Results: Karyotype analysis found 45 (13.2%) abnormal CNS cases, while SNP array found 60 (17.4%) cases. SNP array detected 23 (6.7%) cases of submicroscopic abnormalities that karyotype analysis did not find. The detection rate of karyotype analysis was 8.1% in the group with isolated CNS anomalies, but 16.5% in the group with CNS abnormalities plus extra ultrasound anomalies. Detection rates of SNP array were 12.4% and 20.8% in these two groups, respectively. Statistical analysis showed that the detection rates of both methods were significantly higher in the group with CNS malformations and other ultrasound anomalies than in the group with isolated CNS anomalies. Abnormal chromosomes were detected most frequently in fetuses with holoprosencephaly.Conclusion: Genome-wide SNP array technology can significantly improve the positive detection rate of fetuses with CNS abnormalities. Combining karyotype analysis and SNP array technology is recommended for detecting the development of fetuses with abnormal CNS.Keywords: central nervous system abnormalities, chromosome, karyotype analysis, single nucleotide polymorphism microarray, prenatal diagnosis

(1) Background: At diagnosis, multiplemyeloma risk estimation includes disease burden, end-organ damage, and biomarkers, with increasing emphasis on genetic abnormalities. Multicolor flow cytometry (MFC) is not always considered in risk estimation. We demonstrate associations found between genetic abnormalities and antigen expression of plasma cells measured by MFC. (2) Methods: Single nucleotide polymorphism microarray (SNP-A) karyotyping as well as MFC using standardized next-generation flow (NGF) panels and instrument settings were performed from bone marrow aspirates at the time of diagnosis. (3) Results: We uncovered specific immunophenotype features related to different genetic risk factors. Specifically, we found higher malignant/normal plasma cell ratio and lower expression of CD27, CD38, CD45, CD56, CD117 and CD138 in higher-risk genetic groups or risk categories.

Introduction: Microdeletion syndrome is characterized by sub-microscopic chromosomal deletion smaller than 5 Million bp (5Mb) and frequently associated with multiple congenital anomalies. Fluorescent In Situ Hybridization (FISH), Multiplex Ligation-Dependent Probe Amplification (MLPA), Quantitative Fluorescence Polymerase Chain Reaction (QFPCR), array Comparative Genomic Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) microarray and Next-Generation Sequencing (NGS) techniques are commonly used for precise genetic diagnosis of microdeletion syndrome. Aim: To study the role of mosaicism for the causation of phenotypic heterogeneity in 22q11.2 microdeletion syndrome. Materials and Methods: In this study, for over the period of 10 years, we worked on detection of 22q11.2 microdeletion and observed mosaicism frequently. FISH analysis was used to assess level of mosaicism in metaphase and interphase cells derived from peripheral blood culture (lymphocytes) and interphase cells of various tissues like blood nucleated cells (mesodermal origin), buccal cells (ectodermal origin) and urinary exfoliated cells (endodermal origin). We have also used SNP microarray and QF PCR for further characterization. Results: Among 257 cases of clinically suspected 22q11.2 microdeletion syndrome, presence of 22q11.2 microdeletion was confirmed in 39 cases (15.2%) by FISH. Eleven of 22q11.2 microdeletion cases (28.2%) were found to have mosaicism. We report high (28.2%) prevalence of mosaicism in 22q11.2 microdeletion syndrome and often (about 36% cases) low grade mosaicism (

Introduction: Microdeletion syndrome is characterized by sub-microscopic chromosomal deletion smaller than 5 Million bp (5Mb) and frequently associated with multiple congenital anomalies. Fluorescent In Situ Hybridization (FISH), Multiplex Ligation-Dependent Probe Amplification (MLPA), Quantitative Fluorescence Polymerase Chain Reaction (QFPCR), array Comparative Genomic Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) microarray and Next-Generation Sequencing (NGS) techniques are commonly used for precise genetic diagnosis of microdeletion syndrome. Aim: To study the role of mosaicism for the causation of phenotypic heterogeneity in 22q11.2 microdeletion syndrome. Materials and Methods: In this study, for over the period of 10 years, we worked on detection of 22q11.2 microdeletion and observed mosaicism frequently. FISH analysis was used to assess level of mosaicism in metaphase and interphase cells derived from peripheral blood culture (lymphocytes) and interphase cells of various tissues like blood nucleated cells (mesodermal origin), buccal cells (ectodermal origin) and urinary exfoliated cells (endodermal origin). We have also used SNP microarray and QF PCR for further characterization. Result: Among 257 cases of clinically suspected 22q11.2 microdeletion syndrome, presence of 22q11.2 microdeletion was confirmed in 39 cases (15.2%) by FISH. Eleven of 22q11.2 microdeletion cases (28.2%) were found to have mosaicism. We report high (28.2%) prevalence of mosaicism in 22q11.2 microdeletion syndrome and often (about 36% cases) low grade mosaicism (<35% deleted cells). Outsourced SNP microarray failed to detect low grade mosaicism. We also observed wide variations in deleted cell concentration amongst various tissues (blood, buccal and urinary cells). Conclusion: We conclude that mosaicism in 22q11.2 microdeletion is common (28.2%) and interphase FISH should be the choice of test for detecting mosaicism. [ABSTRACT FROM AUTHOR]

Whole-chromosome aneuploidy screening has become a common practice to improve outcomes and decrease embryonic transfer order in patients undergoing treatment for infertility through in vitro fertilization. Despite implementation of this powerful technology, a significant percentage of euploid embryos fail to result in successful deliveries. As technology has evolved, detection of subchromosomal imbalances and embryonic mosaicism has become possible, and these serve as potential explanations for euploid embryo transfer failures. Cases involving a parent with a balanced translocation provide a unique opportunity to characterize the capabilities and limitations of detecting segmental imbalances with a variety chromosome screening platforms. Adaptation of these methods to de novo imbalances now represent an ongoing challenge in the field of preimplantation genetic screening as additional factors including mosaicism, clinical predictive value, and distinguishing true imbalances from technical artifacts must be more carefully considered. [ABSTRACT FROM AUTHOR]

Background Copy Number Variants (CNVs) is a new molecular frontier in clinical genetics. CNVs in 1p36 are usually pathogenic and have attracted the attention of cytogeneticists worldwide. None of 1p36 triplication has been reported thus far. Results We present three patients with CNVs in 1p36. Among them one is the first 1p36 tetrasomy due to a pure microtriplication and the other two are 1p36 microdeletion. Traditional chromosome G-banding technique showed a normal karyotype. Single nucleotide polymorphism (SNP) microarray analysis combined with multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to identify and confirm the chromosome microdeletion/microtriplication. The facial dysmorphisms of the patient with 1p36 tetrasomy differed from those two patients with 1p36 monosomy. The expression levels of B3GALT6, MIB2, PEX10 and PANK4 in the blood were determined, and differential expressions were observed between the patients and controls. Conclusions Our study shows the first case of 1p36 tetrasomy due to a pure microtriplication in a patient with severe intellectual disability and seizures. The study provides a new resource for studying the mechanisms of microtriplication formation, and provides an evidence that overexpression of the specific genes might be related the specific phenotype of 1p36 microtriplication. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease. The methods currently used for monitoring CLL and determining conditions for treatment are limited in their ability to predict disease progression, patient survival, and response to therapy. Although clonal diversity and the acquisition of new chromosomal abnormalities during the disease course (clonal evolution) have been associated with disease progression, their prognostic potential has been underappreciated because cytogenetic and fluorescence in situ hybridization (FISH) studies have a restricted ability to detect genomic abnormalities and clonal evolution. We hypothesized that whole genome analysis using high resolution single nucleotide polymorphism (SNP) microarrays would be useful to detect diversity and infer clonal evolution to offer prognostic information. In this study, we used the Infinium Omni1 BeadChip (Illumina, San Diego, CA) array for the analysis of genetic variation and percent mosaicism in 25 non-selected CLL patients to explore the prognostic value of the assessment of clonal diversity in patients with CLL. We calculated the percentage of mosaicism for each abnormality by applying a mathematical algorithm to the genotype frequency data and by manual determination using the Simulated DNA Copy Number (SiDCoN) tool, which was developed from a computer model of mosaicism. At least one genetic abnormality was identified in each case, and the SNP data was 98% concordant with FISH results. Clonal diversity, defined as the presence of two or more genetic abnormalities with differing percentages of mosaicism, was observed in 12 patients (48%), and the diversity correlated with the disease stage. Clonal diversity was present in most cases of advanced disease (Rai stages III and IV) or those with previous treatment, whereas 9 of 13 patients without detected clonal diversity were asymptomatic or clinically stable. In conclusion, SNP microarray studies with simultaneous evaluation of genomic alterations and mosaic distribution of clones can be used to assess apparent clonal evolution via analysis of clonal diversity. Since clonal evolution in CLL is strongly correlated with disease progression, whole genome SNP microarray analysis provides a new comprehensive and reliable prognostic tool for CLL patients. [Copyright &y& Elsevier]

Aim: To introduce an approach for the detection of putative genetic host factors that predispose patients to develop head and neck squamous cell carcinomas (HNSCC)., Methods: HNSCC most often result from the accumulation of somatic gene alterations found in tumor cells. A cancer-predisposing genetic background must be expected in individuals who develop multiple cancers, starting at an unexpectedly young age or with little carcinogen exposure. Genome-wide loss of heterozygosity (LOH) profiling by single nucleotide polymorphism microarray mapping was performed in a patient with a remarkable history of multifocal HNSCC., Results: Regions of genomic deletions in germline DNA were identified on several chromosomes with a remarkable size between 1.6 Mb and 8.1 Mb (mega base-pair). No LOH was detected at the genomic location of the tumor suppressor gene P53., Conclusion: Specific patterns of germline DNA deletions may be responsible for susceptibility to HNSCC and should be further analyzed.