Molecular Cytogenetics最新文献

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.

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.

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).

Background: 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.

Case presentation: We report a 9-year-old boy with congenital scapular deformity, iris and chorioretinal coloboma, normal intelligence, and a history of mild motor development delay. The karyotype showed a de novo large 11q deletion. Fluorescence in situ hybridization (FISH) confirmed that the deletion is interstitial, and array comparative genomic hybridization (aCGH) revealed a loss of 25.8 Mb encompassing the 11q14.1-q22.3 region.

Conclusions: The present case and the literature review of 61 previously published cases highlight the clinical heterogeneity and the lack of genotype-phenotype correlation in interstitial 11q deletions. Sprengel's deformity found in our patient might be a new finding in 11q deletions or, more probably, a fortuitous association.

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.

Background: 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.

Case presentation: Here we report two interphase FISH results, which were false-positive for XXY in cytogenetically normal XX individuals. Both false-positive cases were due to hybridization of the Y chromosome centromeric probe DYZ3 to the pericentromeric region of chromosome 15. In both cases, chromosomal microarray revealed no detectable Y chromosome material, suggesting the hybridizations of the DYZ3 probe to chromosome 15 likely represent benign heterochromatic variants of no clinical significance. In one case, the DYZ3 hybridization was also identified in the phenotypically unaffected mother, further suggesting this is likely a rare variant of no clinical significance.

Conclusions: This report marks the first documentation of hybridization of the DYZ3 probe to another chromosome in cytogenetically normal individuals. Our report has important clinical implications, because DYZ3 is widely used by clinical laboratories for Y chromosome detection. Our findings underscore the necessity of confirming abnormal aneuploidy detection FISH results with additional laboratory methods such as chromosomal microarray analysis.

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.

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.