Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages.

 A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023.  This case series of RPL was divided into a single analysis (SA) group of 266 women and a consecutive analysis (CA) group of 225 women with two to three miscarriages analyzed. Of the 269 POC from the SA group and the 469 POC from the CA group, a spectrum of cytogenomic abnormalities of simple aneuploidies, compound aneuploidies, polyploidies, and structural rearrangements/pathogenic copy number variants (pCNVs) were detected in 109 (41%) and 160 cases (34%), five (2%) and 11 cases (2%), 35 (13%) and 36 cases (8%), and 10 (4%) and 19 cases (4%), respectively.

Genotype-Phenotype Correlations for Putative Haploinsufficient Genes in Deletions of 6q26-q27: Report of Eight Patients and Review of Literature.

 Cytogenomic analyses have been used to detect pathogenic copy number variants. Patients with deletions at 6q26-q27 present variable clinical features. We reported clinical and cytogenomic findings of eight unrelated patients with a deletion of 6q26-q27.

Cytogenomic Characterization of Giant Ring or Rod Marker Chromosome in Four Cases of Well-Differentiated and Dedifferentiated Liposarcoma.

Chromosome and array comparative genomic hybridization (aCGH) analyses were performed on two cases of well-differentiated liposarcoma (WDLPS) and two cases of dedifferentiated liposarcoma (DDLPS). The results revealed the characteristic giant ring (GR) or giant rod marker (GRM) chromosomes in all four cases and amplification of numerous somatic copy number alterations (SCNAs) involving a core segment of 12q14.1q15 and other chromosomal regions in three cases.

Detecting regions of homozygosity improves the diagnosis of pathogenic variants and uniparental disomy in pediatric patients.

Chromosomal microarray analysis using single nucleotide polymorphism probes can detect regions of homozygosity (ROH). This confers a potential utility in revealing autosomal recessive (AR) diseases and uniparental disomy (UPD). Results of genetic testing among pediatric patients from 2015 to 2019 were evaluated.

Detection of cytogenomic abnormalities by OncoScan microarray assay for products of conception from formalin-fixed paraffin-embedded and fresh fetal tissues.

Background: The OncoScan microarray assay (OMA) using highly multiplexed molecular inversion probes for single nucleotide polymorphism (SNP) loci enabled the detection of cytogenomic abnormalities of chromosomal imbalances and pathogenic copy number variants (pCNV). The small size of molecular inversion probes is optimal for SNP genotyping of fragmented DNA from fixed tissues. This retrospective study evaluated the clinical utility of OMA as a uniform platform to detect cytogenomic abnormalities for pregnancy loss from fresh and fixed tissues of products of conception (POC).

Cytogenomic Abnormalities in 19 Cases of Salivary Gland Tumors of Parotid Gland Origin.

Salivary gland tumors (SGTs) of parotid origin are a group of diverse neoplasms which are difficult to classify due to their rarity and similar morphologic patterns. Chromosome analysis can detect clonal abnormalities, and array comparative genomic hybridization (aCGH) analysis can define copy number alterations (CNAs) from tumor specimens. Of the 19 cases of various types of SGTs submitted for cytogenomic analyses, an abnormal clone was detected in nine cases (47%), and CNAs were detected in 14 cases (74%).

Monocytic Acute Myeloid Leukemias with KM2TA Translocations to Chromosome 17q that May Clinically Mimic Acute Promyelocytic Leukemia.

Objective: Acute promyelocytic leukemia (APL) with variant RARA translocation, eg, t(11;17), is not sensitive to all-trans retinoic acid and requires distinct chemotherapy. However, there are some leukemic entities that may mimic aspects of the clinical and/or laboratory picture of APL and cause confusion because of karyotype nomenclature. Therefore, recognition of such entities may be of therapeutic and prognostic significance.

Ring chromosome formation by intra-strand repairing of subtelomeric double stand breaks and clinico-cytogenomic correlations for ring chromosome 9.

Constitutional ring chromosome 9, r(9), is a rare chromosomal disorder. Cytogenomic analyses by karyotyping, array comparative genomic hybridization (aCGH) and whole genome sequencing (WGS) were performed in a patient of r(9). Karyotyping detected a mosaic pattern of r(9) and monosomy 9 in 83% and 17% of cells, respectively.

Diagnostic cytogenetic testing following positive noninvasive prenatal screening results of sex chromosome abnormalities: Report of five cases and systematic review of evidence.

Background: Follow-up cytogenetic analysis has been recommended for cases with positive noninvasive prenatal screening (NIPS) results. This study of five cases with numerical and structural sex chromosomal abnormalities (SCA) and a review of large case series of NIPS provided guidance to improve prenatal diagnosis for SCA.

Methods: Following positive NIPS results for SCA, karyotype analysis, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH), and locus-specific quantitative PCR were performed on cultured amniocytes, chorionic villi cells, and stimulated lymphocytes.

A Retrospective Analysis of 10-Year Data Assessed the Diagnostic Accuracy and Efficacy of Cytogenomic Abnormalities in Current Prenatal and Pediatric Settings.

Array comparative genomic hybridization (aCGH), karyotyping and fluorescence hybridization (FISH) analyses have been used in a clinical cytogenetic laboratory. A systematic analysis on diagnostic findings of cytogenomic abnormalities in current prenatal and pediatric settings provides approaches for future improvement. A retrospective analysis was performed on abnormal findings by aCGH, karyotyping, and FISH from 3,608 prenatal cases and 4,509 pediatric cases during 2008-2017.

Inverted duplication, triplication and quintuplication through sequential breakage-fusion-bridge events induced by a terminal deletion at 5p in a case of spontaneous abortion.

Background: Integrated chromosome, fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (aCGH) analyses have been effective in defining unbalanced chromosomal rearrangements. Discordant chromosome and aCGH results are rarely reported.

Methods: Routine cytogenomic analyses and literature review were performed in the study of a case from products of conception (POC).

Analytical validation and chromosomal distribution of regions of homozygosity by oligonucleotide array comparative genomic hybridization from normal prenatal and postnatal case series.

Background: Regions of homozygosity (ROH) are continuous homozygous segments commonly seen in the human genome. The integration of single nucleotide polymorphism (SNP) probes into current array comparative genomic hybridization (aCGH) analysis has enabled the detection of the ROH. However, for detecting and reporting biologically relevant ROH in a clinical setting, it is necessary to assess the analytical validity of SNP calling and the chromosomal distribution of ROH in normal populations.

Integrated FISH, Karyotyping and aCGH Analyses for Effective Prenatal Diagnosis of Common Aneuploidies and Other Cytogenomic Abnormalities.

Current prenatal genetic evaluation showed a significantly increase in non-invasive screening and the reduction of invasive diagnostic procedures. To evaluate the diagnostic efficacy on detecting common aneuploidies, structural chromosomal rearrangements, and pathogenic copy number variants (pCNV), we performed a retrospective analysis on a case series initially analyzed by aneuvysion fluorescence in situ hybridization (FISH) and karyotyping then followed by array comparative genomic hybridization (aCGH). Of the 386 cases retrieved from the past decade, common aneuploidies were detected in 137 cases (35.

Spectrum of Cytogenomic Abnormalities Revealed by Array Comparative Genomic Hybridization on Products of Conception Culture Failure and Normal Karyotype Samples.

Approximately 30% of pregnancies after implantation end up in spontaneous abortions, and 50% of them are caused by chromosomal abnormalities. However, the spectrum of genomic copy number variants (CNVs) in products of conception (POC) and the underlying gene-dosage-sensitive mechanisms causing spontaneous abortions remain largely unknown. In this study, array comparative genomic hybridization (aCGH) analysis was performed as a salvage procedure for 128 POC culture failure (POC-CF) samples and as a supplemental procedure for 106 POC normal karyotype (POC-NK) samples.

Changes in and Efficacies of Indications for Invasive Prenatal Diagnosis of Cytogenomic Abnormalities: 13 Years of Experience in a Single Center.

Background: Because the future application of cell-free fetal DNA screening is expected to dramatically improve the diagnostic yield and reduce unnecessary invasive procedures, it is time to summarize the indications of invasive prenatal diagnosis. This retrospective study was performed to evaluate the changes and efficacies of indications of invasive procedures for detecting cytogenomic abnormalities from 2000 to 2012.

Material And Methods: From our regional obstetric unit, 7818 invasive procedures were referred by indications of advance maternal age (AMA), abnormal ultrasound findings (aUS), abnormal maternal serum screening (aMSS), and family history (FH).

Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia.

Background: To evaluate the clinical validity of genome-wide oligonucleotide array comparative genomic hybridization (aCGH) for detecting somatic abnormalities, we have applied this genomic analysis to 30 cases (13 MDS and 17 AML) with clonal chromosomal abnormalities detected in more than 50% of analyzed metaphase cells.

Results: The aCGH detected all numerical chromosomal gains and losses from the mainline clones and 113 copy number alterations (CNAs) ranging from 0.257 to 102.