Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. Microduplication of 15q21.3 is rare and is associated with an increased risk of developmental retardation, corpus callosum hypoplasia, microcephaly, cardiomyopathy, optic nerve hypoplasia and so on. Microduplication of 16p11.2 is associated with 16p11.2 microduplication syndrome (OMIM: 614671). The main clinical manifestations are low birth weight, microcephaly, mental retardation, language retardation, abnormal behavior, attention deficit, schizophrenia, affective disorder, loneliness spectrum disorder and so on. Individuals who carry these two microduplications are even more rare.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, comprising approximately 25% of pediatric malignancies. Notably, chromosomal aberrations and genetic alterations play a central role in the pathogenesis of ALL, serving as critical diagnostic and prognostic markers. In this study, we use array-based comparative genomic hybridization (array-CGH) to explore the landscape of copy number variations (CNVs) and variants of uncertain significance (VUS) in 67 Malaysian childhood ALL patients with normal karyotype.

Lynch syndrome is an autosomal dominant disorder predisposing individuals to colorectal and other cancers, primarily caused by variants in mismatch repair genes. This study describes a novel MSH6 variant affecting transcript structure in a Taiwanese family meeting the Amsterdam II criteria for Lynch syndrome. A 67-year-old male presented with jejunal adenocarcinoma and a strong family history of colorectal cancer. Immunohistochemistry revealed loss of MSH6 expression, while next-generation sequencing performed on tumor tissue failed to detect any MSH6 variants. Comprehensive genetic analysis, including RT-PCR and Sanger sequencing of both cDNA and genomic DNA, identified a novel exon 5-6 skipping variant in the MSH6 gene transcript (NM_000179.3:r.3262_3645del), linked to a 2268 bp deletion from the 3' portion of intron 4 to the middle of intron 6 of the MSH6 gene (NC_000002.12:g.47803007_47805274del). This variant was also detected in two of the patient's asymptomatic sons, highlighting its heritability and potential cancer predisposition. The study emphasizes the limitations of capture-enrichment NGS panels in detecting certain types of variants and underscores the value of orthogonal confirmation using cDNA analysis for transcript aberrations. The identification of this novel variant expands our understanding of Lynch syndrome's mutational spectrum and has implications for genetic diagnosis and counseling. Based on these findings, the patient was treated with pembrolizumab, resulting in stable disease for 8 months. This case highlights the importance of comprehensive genetic approaches in suspected Lynch syndrome cases and the potential utility of mRNA-based screening as an additional method when NGS analysis is negative and the clinical presentation strongly suggests Lynch syndrome.

Telomere in cancers shows a main impact on maintaining chromosomal stability and unlimited proliferative capacity of tumor cells to promote cancer development and progression. So, we targeted to detect telomere-related genes(TRGs) in hepatocellular carcinoma (HCC) to develop a novel predictive maker and response to immunotherapy. We sourced clinical data and gene expression datasets of HCC patients from databases including TCGA and GEO database. The TelNet database was utilized to identify genes associated with telomeres. Genes with altered expression from TCGA and GSE14520 were intersected with TRGs, and Cox regression analysis was conducted to pinpoint genes strongly linked to survival prognosis. The risk model was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression technique. Subsequently, evaluation of the risk model focused on immune cell infiltration, checkpoint genes, drug responsiveness, and immunotherapy outcomes across both high- and low-risk patient groups. We obtained 25 TRGs from the overlapping set of 34 genes using Cox regression analysis. Finally, six TRGs (CDC20, TRIP13, EZH2, AKR1B10, ESR1, and DNAJC6) were identified to formulate the risk score (RS) model, which independently predicted prognosis for HCC. The high-risk group demonstrated worse survival outcomes and showed elevated levels of infiltration by Macrophages M0 and Tregs. Furthermore, a notable correlation was observed between the genes in the risk model and immune checkpoint genes. The RS model, derived from TRGs, has been validated for its predictive value in immunotherapy outcomes. In conclusion, this model not only predicted the prognosis of HCC patients but also their immune responses, providing innovative strategies for cancer therapy.

Carriers of balanced reciprocal translocation are usually phenotypically normal; however, they have an increased risk of producing gametes with chromosomal imbalance through different types of meiotic segregation of the translocation quadrivalent. The genetically imbalanced gametes when they survive can result in embryos with chromosomal abnormalities. Here we report a family with two siblings inheriting partial trisomy for 9p and 18p concurrently resulting from a 3:1 meiotic segregation of a maternal balanced translocation involving chromosome 9q and 18p, and the associated phenotype.

The saffron-producing Crocus sativus (L.) and its wild relative C. cartwrightianus (Herb.) are key species for understanding genetic evolution in this genus. Molecular-cytogenetic methods, especially fluorescent in situ hybridization (FISH), are essential for exploring the genetic relationships in this genus. Yet, preparing high-quality chromosomes for FISH analysis across Crocus species remains difficult. A standardized protocol for achieving clear and well-separated mitotic chromosomes is still lacking. This study aimed to assess the effectiveness of pretreatments with four chromosome synchronization methods for optimal chromosome spread preparation in Crocus. Root tips of different Crocus species were treated with four chromosome preparation methods namely hydroxyurea-colchicine (HC), nitrous oxide (NO), hydroxyquinoline (HQ), and ice water (IW) pretreatments to investigate their effectiveness in producing high-quality mitotic chromosome spreads. Metaphases obtained by the four methods were analyzed to assess their quality and metaphase index.

The X chromosome is enriched with genes related to brain development, and the hemizygous state of these genes in men causes some difficulties in the clinical interpretation of copy number variations (CNVs). In this study, we present data on the frequency and spectrum of CNVs on the X chromosome in a cohort of patients with neurodevelopmental disorders (NDDs).

Gestational trophoblastic neoplasms consist of complete and partial hydatidiform moles, both of which are considered aberrant conceptuses. Both conditions, complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM), differ in histological characteristics, genetic origin and content and clinical features. CHM have a diploid karyotype, mostly 46,XX but lack maternal genetic contribution with all chromosomes of paternal origin. High-resolution SNP microarray testing is an efficient method used to determine the parental contribution of the genomic material in molar pregnancies and confirm the diagnosis.

Thalassemia is an autosomal recessive genetic disorder and a common form of Hemoglobinopathy. It is classified into α-thalassemia and β-thalassemia. This disease is mainly prevalent in tropical and subtropical regions, including southern China. Severe α-thalassemia and intermediate α-thalassemia are among the most common birth defects in southern China. Intermediate α-thalassemia, also known as Hb H disease, is characterized by moderate anemia. Severe α-thalassemia, also known as Hb Bart's Hydrops fetalis syndrome, is a fatal condition. Infants with severe β-thalassemia do not show symptoms at birth but develop severe anemia later, requiring expensive treatment. Most untreated patients with severe β-thalassemia die in early childhood. Screening for thalassemia carriers and genetic diagnosis in high-prevalence areas significantly reduce the incidence of severe thalassemia. This review aims to summarize the genetic diagnostic approaches for thalassemia. Conventional genetic testing methods can identify 95-98% of thalassemia carriers but may miss rare thalassemia genotypes. Third-Generation Sequencing offers significant advantages in complementing other genetic diagnostic approaches, providing a basis for genetic counseling and prenatal diagnosis.

The advent of non-invasive prenatal testing (NIPT) in the screening of fetal abnormalities has optimized prenatal care and decreased the rate of invasive diagnostic tests. In this retrospective descriptive study, we began with 1874 singleton pregnancies. After exclusion of some cases, the study cohort ended up with 1674 cases. We analyzed the performance of NIPT based on the results of first trimester screening (FTS) using serum screening combined with NT. The cases were also compared to diagnostic testing/pregnancy outcomes. Notably, in the subgroup with FTS risk < 1000, NIPT was reported to be normal in all cases with no false negative results. In the risk group of 1/300-1/1000, NIPT could detect all trisomy 21 cases with one false positive result. Moreover, in the risk group of 1/11 - 1/300, NIPT could detect all cases of trisomy 21, 13 and 18 with low false positive rate. However, the false positive rate for sex chromosomal abnormalities was high. Taken together, the current study confirms the applicability of NIPT as a tool for detection of fetal trisomies with high sensitivity and specificity. Yet, the high rate of false positive results for sex chromosome abnormalities should be considered in the interpretation of the results.

Interstitial chromosome 11 long arm deletions (11q13-q23) represent a rare cytogenetic abnormality characterized by non-specific clinical features including intellectual disability and several malformations without a clear genotype-phenotype correlation. We describe the first case of interstitial 11q deletion identified in a boy with Sprengel's deformity and provide a review of the literature.

Ring chromosome 18 (r(18)) is a rare chromosomal abnormality characterized by the circular rearrangement of chromosome 18, which presents significant challenges in genotype-phenotype correlations due to variability in deletions across the 18p and 18q arms. We report the case of a pediatric patient with a de novo ring chromosome 18, diagnosed by karyotype analysis and confirmed by high-resolution SNP arrays. The patient exhibited pathogenic copy number variants (CNVs) in the 18p11.32p11.22 and 18q23 regions, involving 36 and 10 OMIM genes, respectively. Clinically, the patient presented with hypothyroidism secondary to autoimmune thyroiditis, autoimmune hepatitis type II, and genetic predisposition to celiac disease and insulin-dependent diabetes mellitus (IDDM) along with notable dysmorphic features. The 18q microdeletion encompasses the MBP gene, involved in the development and functionality of the nervous system, as supported by hypotonia and gliosis shown by the MRI. This case highlights the complex interplay between genetic imbalances on chromosome 18 and autoimmune phenotypes, emphasizing the need for ongoing research to elucidate underlying mechanisms and optimize clinical management for individuals with r(18).

Cancers are heterogeneous diseases with unifying features of abnormal and consuming cell growth, where the deregulation of normal cellular functions is initiated by the accumulation of genomic mutations in cells of - potentially - any organ. At diagnosis malignancies typically present with patterns of somatic genome variants on diverse levels of heterogeneity. Among the different types of genomic alterations, copy number variants (CNV) represent a distinct, near-ubiquitous class of structural variants. Cancer classifications are foundational for patient care and oncology research. Terminologies such as the National Cancer Institute Thesaurus provide large sets of hierarchical cancer classification vocabularies and promote data interoperability and ontology-driven computational analysis. To find out how categorical classifications correspond to genomic observations, we conducted a meta-analysis of inter-sample genomic heterogeneity for classification hierarchies on CNV profiles from 97,142 individual samples across 512 cancer entities, and evaluated recurring CNV signatures across diagnostic subsets. Our results highlight specific biological mechanisms across cancer entities with the potential for improvement of patient stratification and future enhancement of cancer classification systems and provide some indications for cooperative genomic events across distinct clinical entities.

Interphase fluorescence in situ hybridization (FISH) is commonly used for rapid aneuploidy detection in clinical settings. While FISH-based aneuploidy detection provides rapid results desirable for patient management, it usually only utilizes one probe per chromosome, which may lead to rare false-positive findings.

In recent years, the expansion of molecularly targeted cancer therapies has significantly advanced precision oncology. Parallel developments in next-generation sequencing (NGS) technologies have also improved precision oncology applications, making genomic analysis of tumors more affordable and accessible. Targeted NGS panels now enable the rapid identification of diverse actionable mutations, requiring clinicians to efficiently assess the predictive value of cancer biomarkers for specific treatments. The urgency for timely and accurate decision-making in oncology emphasizes the importance of reliable precision oncology software. Online clinical decision-making tools and associated cancer databases have been designed by consolidating genomic data into standardized, accessible formats. These new platforms are highly integrated and crucial for identifying actionable somatic genomic biomarkers essential for tumor survival, determining corresponding drug targets, and selecting appropriate treatments based on the mutational profile of each patient's tumor. To help oncologists and translational cancer researchers unfamiliar with these tools, we review the utility, accuracy, and comprehensiveness of several commonly used precision medicine software options currently available. Our analysis categorized selected genomic databases based on their primary content, utility, and how well they provide practical guidance for interpreting somatic biomarker data. We identified several comprehensive, mostly open-access platforms that are easy to use for genetic biomarker searches, each with unique features and limitations. Among the precision oncology tools we evaluated, we found MyCancerGenome and OncoKB to be the first choice, offering comprehensive, accurate up-to-date information on the clinical significance of somatic mutations. To illustrate the application of these precision oncology tools in clinical settings, we evaluated three case studies to see how use of the platforms could have influenced treatment planning. Most of the precision oncology software evaluated could be easily streamlined into clinical workflows to provide updated information on approved drugs and clinical trials related the actionable mutations detected. Some platforms were very intuitive and easy to use, while others, often developed in smaller academic settings, were more difficult to navigate and may not be updated consistently. Future enhancements, incorporating artificial intelligence algorithms, are likely to improve integration of the platforms with diverse big data sources, enabling more accurate predictions of potential therapeutic responses.

We present the case of a 7-year-old Ecuadorian mestizo girl with multiple orofacial malformations. The patient is the product of a first-degree relationship (father-daughter). A cytogenetic study revealed a normal karyotype. The genetic mapping array study identified 0.73 Gb of alterations, 727,087,295 bp involved in regions of homozygosity (ROH) in all chromosomes (25.2% of the genome) and 764,028 bp in gains in chromosomes 9 and 14. Genes from the TGFB, BMP, FGF, SHH and WNT families, among others, were identified in the ROH. They are related to craniofacial development and their protein products showed a strong association in the interactome analysis.

In last 100 years or so, much information has been accumulated on avian karyology, genetics, physiology, biochemistry and evolution. The chicken genome project generated genomic resources used in comparative studies, elucidating fundamental evolutionary processes, much of it funded by the economic importance of domestic fowl (which are also excellent model species in many areas). Studying karyotypes and whole genome sequences revealed population processes, evolutionary biology, and genome function, uncovering the role of repetitive sequences, transposable elements and gene family expansion. Knowledge of the function of many genes and non-expressed or identified regulatory components is however still lacking. Birds (Aves) are diverse, have striking adaptations for flight, migration and survival and inhabit all continents most islands. They also have a unique karyotype with ~ 10 macrochromosomes and ~ 30 microchromosomes that are smaller than other reptiles. Classified into Palaeognathae and Neognathae they are evolutionarily close, and a subset of reptiles. Here we overview avian molecular cytogenetics with reptilian comparisons, shedding light on their karyotypes and genome structure features. We consider avian evolution, then avian (followed by reptilian) karyotypes and genomic features. We consider synteny disruptions, centromere repositioning, and repetitive elements before turning to comparative avian and reptilian genomics. In this context, we review comparative cytogenetics and genome mapping in birds as well as Z- and W-chromosomes and sex determination. Finally, we give examples of pivotal research areas in avian and reptilian cytogenomics, particularly physical mapping and map integration of sex chromosomal genes, comparative genomics of chicken, turkey and zebra finch, California condor cytogenomics as well as some peculiar cytogenetic and evolutionary examples. We conclude that comparative molecular studies and improving resources continually contribute to new approaches in population biology, developmental biology, physiology, disease ecology, systematics, evolution and phylogenetic systematics orientation. This also produces genetic mapping information for chromosomes active in rearrangements during the course of evolution. Further insights into mutation, selection and adaptation of vertebrate genomes will benefit from these studies including physical and online resources for the further elaboration of comparative genomics approaches for many fundamental biological questions.

Right aortic arch (RAA) is a common congenital aortic arch abnormality. Fetuses with RAA frequently have good outcomes after birth. However, chromosomal abnormalities and genetic syndromes suggest poor prognosis for these patients. So far the underlying genetic etiology is still not identified in most RAA patients based on traditional genetic techniques and a problem is still debated whether fetuses with isolated RAA should be referred for CMA. Our study aims to investigate the genetic etiology of fetuses with right aortic arch (RAA) by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) and evaluate the efficacy of CMA in fetal isolated RAA.

The karyotype is a major determinant of prognosis in myelodysplastic syndrome (MDS). Details of the cytogenetic profile of MDS in South Asia are limited because cytogenetic services are not widely available.