Molecular Cytogenetics

BACKGROUND: Many clinical studies based on spontaneous pregnancies (SPs) have demonstrated the superiority of non-invasive prenatal testing (NIPT), and the question of whether this technology is suitable for offspring conceived by assisted reproductive technology has attracted attention. This study aimed to evaluate the application value of NIPT in screening for trisomy (T)21, T18, T13 and sex chromosome aneuploidy (SCA) in pregnant women who conceived by in vitro fertilization (IVF)...

BACKGROUND: Cytogenetic analysis continues to have an important role in the management of acute myeloid leukemia (AML) because it is essential for prognostication. It is also necessary to diagnose specific categories of AML and to determine the most effective form of treatment. Reports from South Asia are few because the availability of cytogenetic services is relatively limited. METHODS: We performed a retrospective analysis of the cytogenetic findings in adults with AML seen consecutively in a single centre in India...

BACKGROUND: Small supernumerary marker chromosome (sSMC) is a structurally abnormal chromosome of unknown origin by conventional cytogenetics. The understanding of clinical significance of sSMC is still limited in prenatal diagnosis. The presence of sSMC poses a challenge for genetic counselling. METHODS: We obtained the clinical information of 25 cases with sSMC. The fetal samples were subjected to multiple molecular and cytogenetic approaches including karyotype analysis, chromosomal microarray analysis, bacterial artificial chromosomes-on-beads assay, and fluorescence in situ hybridization...

OBJECTIVE: To evaluate the prenatal and perinatal outcome of fetuses with extremely large nuchal translucency (eNT) thickness (≥ 6.5 mm). METHODS: 193 (0.61%) singleton fetuses with eNT were retrospectively included. Anomaly scan, echocardiography, and chromosomal and genetic test were included in our antenatal investigation. Postnatal follow-up was offered to all newborns. RESULTS: Major congenital anomalies included congenital heart defect (32...

BACKGROUND: Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant disorder caused by mutations in the KMT2A gene and is usually characterized by hairy elbows, short stature, developmental delay, intellectual disability and obvious facial dysmorphism. CASE PRESENTATION: Here, we report a 5-year-old girl with clinical features similar to WDSTS, including postnatal growth delay, retarded intellectual development, and ocular hypertelorism. Through whole-exome sequencing (WES), a frameshift variant of KMT2A was found in the patient but not in her parents' genomic DNA...

Uniparental disomy (UPD) is when all or part of the homologous chromosomes are inherited from only one of the two parents. Currently, UPD has been reported to occur for almost all chromosomes. In this study, we report two cases of UPD for chromosome 2 (UPD2) encountered during prenatal diagnosis. The ultrasound findings of the fetuses from two unrelated families showed intrauterine growth restriction. The karyotype analyses were normal. The two fetuses both had complete paternal chromosome 2 uniparental disomy detected by whole-exome sequencing, but their clinical outcomes were significantly different, with fetal arrest in case 1 and birth in case 2...

BACKGROUND: High expression of the Cytokine Receptor-Like Factor 2 (CRLF2) gene has been observed in patients with acute lymphoblastic leukemia BCR-ABL1-like subtype. Currently, there is no commercial system available for the direct detection of the IGH::CRLF2 fusion by fluorescent in situ hybridization (FISH), as there are for many other leukemia-related gene fusions. In an effort to verify the IGH::CRLF2 fusion, some researchers prepare home-grown FISH probes from bacterial artificial chromosome clones flanking the IGH and CRLF2 genes, which is the best alternative to confirm the fusion, however difficult to reproduce in most cytogenetic laboratories...

BACKGROUND: Isolated terminal 4q35.2 microdeletion is an extremely rare copy number variant affecting people all over the world. To date, researchers still have controversial opinions and results on its pathogenicity. Here, we aim to present a Chinese pediatric patient with terminal 4q35.2 microdeletion and use this case to clarify the underlying genotype-phenotype correlation. METHODS: A 17-year-old boy from Quanzhou, South China, was recruited as the main subject in this study...

INTRODUCTION: A precise diagnosis of central nervous system involvement in acute lymphoblastic leukemia (ALL) requires comprehensive knowledge of morphological analysis, with a focus on the quantity and quality of cells being examined. Some research has utilized techniques such as immunocytochemistry, flow cytometry, polymerase chain reaction (PCR), and interphase fluorescence in situ hybridization (iFISH) on cerebrospinal fluid (CSF) cytospin samples to detect any remaining leukemic cells in the CSF...

BACKGROUND: Non-invasive prenatal testing (NIPT) using cell-free DNA has been widely used for prenatal screening to detect the common fetal aneuploidies (such as trisomy 21, 18, and 13). NIPT has been shown to be highly sensitive and specific in previous studies, but false positives (FPs) and false negatives (FNs) occur. Although the prevalence of FN NIPT results for Down syndrome is rare, the impact on families and society is significant. CASE PRESENTATION: This article described two cases of foetuses that tested "negative" for trisomy 21 by NIPT technology using the semiconductor sequencing platform...

Copy number variants (CNVs) have been identified as common genomic variants that play a significant role in inter-individual variability. Conversely, rare recurrent CNVs have been found to be causal for many disorders with well-established genotype-phenotype relationships. However, the phenotypic implications of rare non-recurrent CNVs remain poorly understood. Herein, we re-investigated 18,542 cases reported from chromosomal microarray at Greenwood Genetic Center from 2010 to 2022 and identified 15 cases with CNVs involving the 17q25...

BACKGROUND: With the application of chromosome microarray, next-generation sequencing and other highly sensitive genetic techniques in disease diagnosis, the detection of mosaicism has become increasingly prevalent. This study involved a retrospective analysis of SNP array testing on 4512 prenatal diagnosis samples, wherein the characterization of mosaicism was explored and insights were gained into the underlying mechanisms thereof. RESULTS: Using SNP array, a total of 44 cases of mosaicism were identified among 4512 prenatal diagnostic cases; resulting in a detection rate of approximately 1...

BACKGROUND: Anqing six-end-white pig is a native breed in Anhui Province. The pigs have the disadvantages of a slow growth rate, low proportion of lean meat, and thick back fat, but feature the advantages of strong stress resistance and excellent meat quality. Duroc pig is an introduced pig breed with a fast growth rate and high proportion of lean meat. With the latter breed featuring superior growth characteristics but inferior meat quality traits, the underlying molecular mechanism that causes these phenotypic differences between Chinese and foreign pigs is still unclear...

BACKGROUND: BCR::ABL1-like acute lymphoblastic leukaemia (BCR::ABL1-like ALL) is characterized by inferior outcomes. Current efforts concentrate on the identification of molecular targets to improve the therapy results. The accessibility to next generation sequencing, a recommended diagnostic method, is limited. We present our experience in the BCR::ABL1-like ALL diagnostics, using a simplified algorithm. RESULTS: Out of 102 B-ALL adult patients admitted to our Department in the years 2008-2022, 71 patients with available genetic material were included...

BACKGROUND: Copy-number variants (CNVs) drive many neurodevelopmental-related disorders. Although many neurodevelopmental-related CNVs can give rise to widespread phenotypes, it is necessary to identify the major genes contributing to phenotypic presentation. Copy-number variations in chromosome 6, such as independent 6p deletion and 6p duplication, have been reported in several live-born infants and present widespread abnormalities such as intellectual disability, growth deficiency, developmental delay, and multiple dysmorphic facial features...

BACKGROUND: Noninvasive prenatal testing (NIPT) allows for screening of fetal aneuploidy and copy number variants (CNVs) from cell-free DNA (cfDNA) in maternal plasma. Professional societies have not yet embraced NIPT for fetal CNVs, citing a need for additional performance data. A clinically available genome-wide cfDNA test screens for fetal aneuploidy and CNVs larger than 7 megabases (Mb). RESULTS: This study reviews 701 pregnancies with "high risk" indications for fetal aneuploidy which underwent both genome-wide cfDNA and prenatal microarray...

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare, autosomal recessive, hereditary neurodegenerative disorder. It is characterized mainly by early onset progressive encephalopathy, concomitant with an increase in interferon-α levels in the cerebrospinal fluid. Preimplantation genetic testing (PGT) is a procedure that could be used to choose unaffected embryos for transfer after analysis of biopsied cells, which prevents at-risk couples from facing the risk of pregnancy termination...

BACKGROUND: Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder characterized by the development of multiple, circumscript and usually symmetric bony protuberances called osteochondromas. Most HME are caused by EXT1 and EXT2 loss of function mutations. Most pathogenic mutations are nonsense followed by missense mutations and deletions. CASE PRESENTATION: Here we report on a patient with a rare and complex genotype resulting in a typical HME phenotype...

BACKGROUND: X/Y translocations are highly heterogeneity in terms of clinical genetic effects, and most patients lack complete pedigree analysis for clinical and genetic characterization. RESULTS: This study comprehensively analyzed the clinical and genetic characteristics of three new patients with X/Y translocations. Furthermore, cases with X/Y translocations reported in the literature and studies exploring the clinical genetic effects in patients with X/Y translocations were reviewed...

Trisomy 21 (Down syndrome) is the most common autosomal aneuploidy among newborns. About 90% result from meiotic nondisjunction during oogenesis, which occurs around conception, when also the most profound epigenetic modifications take place. Thus, maternal meiosis is an error prone process with an extreme sensitivity to endogenous factors, as exemplified by maternal age. This contrasts with the missing acceptance of causal exogenous factors. The proof of an environmental agent is a great challenge, both with respect to ascertainment bias, determination of time and dosage of exposure, as well as registration of the relevant individual health data affecting the birth prevalence...