Estimating the frequency of causal genetic variants in foetuses with congenital heart defects: a Chinese cohort study

Background The belief that genetics plays a major role in the pathogenesis of congenital heart defects (CHD) has grown popular among clinicians. Although some studies have focused on the genetic testing of foetuses with CHD in China, the genotype–phenotype relationship has not yet been fully established, and hotspot copy number variations (CNVs) related to CHD in the Chinese population are still unclear. This cohort study aimed to assess the prevalence of chromosomal abnormalities in Chinese foetuses with different types of CHD. Results In a cohort of 200 foetuses, chromosomal abnormalities were detected in 49 (24.5%) after a prenatal chromosome microarray analysis (CMA), including 23 foetuses (11.5%) with aneuploidies and 26 (13.0%) with clinically significant CNVs. The additional diagnostic yield following whole exome sequencing (WES) was 11.5% (6/52). The incidence of total chromosomal abnormality in the non-isolated CHD group (31.8%) was higher than that in the isolated CHD group (20.9%), mainly because the incidence of aneuploidy was significantly increased when CHD was combined with extracardiac structural abnormalities or soft markers. The chromosomal abnormality rate of the complex CHD group was higher than that of the simple CHD group; however, the difference was not statistically significant (31.8% vs. 23.6%, P = 0.398). The most common CNV detected in CHD foetuses was the 22q11.2 deletion, followed by deletions of 5p15.33p15.31, deletions of 15q13.2q13.3, deletions of 11q24.2q25, deletions of 17p13.3p13.2, and duplications of 17q12. Conclusions CMA is the recommended initial examination for cases of CHD in prenatal settings, for both simple heart defects and isolated heart defects. For cases with negative CMA results, the follow-up application of WES will offer a considerable proportion of additional detection of clinical significance.

Prevalence of common aneuploidy in twin pregnancies

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04–0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Proposal of Algorithm for Automated Chromosomal Abnormality Detection

The article considers the problem of automatic chromosome abnormalities recognition, using images of chromosomes as an input. This paper’s scope includes overview of application domain and analysis of existing solutions. A high-level algorithm for chromosome abnormalities recognition automation is proposed, and a proof-of-concept application is built on top of the algorithm.

Idiopathic pigmented gingival fibromatosis: A case report

Gingival fibromatosis is a rare and heterogeneous group of disorders that develop as slowly progressive, local or diffuse enlargements within marginal and attached gingiva or interdental papilla. Gingival fibromatosis is a condition that can occur as an isolated disease or as a part of a syndrome or chromosomal abnormality. Here, we present the case of a 28-year-old male with pigmented gum enlargement in the maxilla and mandible. The clinical, radiographic, and histopathological features have been described in detail.

Multiple subpleural cysts in the lungs in a child with Down’s syndrome

Down’ssyndrome is the most common chromosomal abnormality in live births. Due to the complete or partialtrisomy of chromosome 21the Down’s syndrome causes cognitive impairment, dysmorphic features and congenital mal formations. Pulmonary disease is the most common cause of death in patients with Down’s syndrome. The article highlights the pulmonological problems of the patients, and it also describes a clinical case of a child with Down’s syndrome with pulmonary pathology.

Chromosomal Analysis of 129 Miscarried Conceptuses: A Retrospective Study

Background Embryonic chromosomal abnormality is one of the significant causative factors of pregnancy loss. Our goal was to investigate the differences of chromosomal abnormality between different conception modes in miscarried products of conception (POCs). Methods A retrospective study included 129 miscarried POCs from 81 women undergoing assisted reproductive technology (ART) and 48 spontaneous pregnant (SP) women during March 2019 to March 2021 in Renmin Hospital of Wuhan University. Subgroups were divided according to age, fertilization method, types of embryo transfer. The profiles of cytogenetic abnormalities in the miscarried POCs were measured via next-generation sequencing. Results The total chromosomal abnormality rate was 65.1%. No significant difference was found in the rate of chromosomal abnormalities between ART and SP group (63% vs. 68.8%, P = 0.505). However, the rate of chromosomal structural abnormalities was significantly increased in ART group (P = 0.02). There was no significant difference in the rate of chromosomal abnormalities when stratified by age (62.9% vs. 71.9%, P = 0.355) and frequency of abortion (66.7% vs. 63.2%, P = 0.678). In the patients aged < 35 years, the ART group had more frequent structural abnormality than SP group (P = 0.006). In the patients aged ≥ 35 years, numerical chromosomal abnormality was predominated in both groups (P = 0.655). Compared with the IVF fertilization subgroup, microdeletion was more frequent in the ICSI fertilization subgroup (80% vs.28.6%, P = 0.013). The rate of chromosomal abnormality in the fresh embryo transfer group was significantly higher than that in the frozen embryo transfer group (92.3% vs.50%, P = 0.0001), especially the structural abnormality (46.2% vs. 15.4%, P = 0.016). Conclusion Chromosomal abnormality is the main cause of spontaneous abortion, whether in SP or in ART patients. The incidence of structural abnormalities in miscarried POCs from ART patients was significantly increased and fresh cycles had higher frequency of chromosomal abnormalities than the frozen cycles, hints us that “freezing all” should be considered in the process of assisted reproduction if encountered hyper ovarian stimulation, to avoid the negative effect of high estrogen environment on embryo development.

Euploid First-Trimester Cystic Hygroma: A More Benign Entity than Previously Thought?

<b><i>Objective:</i></b> Studies summarizing the outcome of first-trimester septated cystic hygroma are generally based on small studies or from multiple centers with limited ascertainment. We reviewed the natural history of a large cohort of such cases from a single tertiary referral center, with the aim being to establish contemporary outcome data, particularly in the setting of normal karyotype. <b><i>Methods:</i></b> A retrospective cohort study from 2007 to 2017 was conducted at a single tertiary referral prenatal diagnosis center. Data were analyzed from a prospectively collated fetal anomaly database. Search terms were “increased nuchal translucency (NT),” “cystic hygroma,” and “septated cystic hygroma.” All cases were confirmed to have NT &#x3e;3 mm with septations. Cases of simple increased NT without septations were excluded. <b><i>Results:</i></b> During the study period, over 110,000 pregnancies were delivered at our center, resulting in 410 cases of septated cystic hygroma diagnosed prior to 14 weeks’ gestation. Pregnancy outcome was obtained in 99% (405/410) of cases, with detailed pathology outcome available in 92% (378/410). A total of 87% (351/405) underwent invasive prenatal testing, and postnatal chromosome status was established in further 27 cases. A total of 61% (230/378) had abnormal chromosomal status. Of the 39% (148/378) with normal chromosomal status, only 13% (19/148) had a significant structural fetal abnormality, which included 7 cardiac and 12 noncardiac abnormalities. Overall, the perinatal loss was 62% (253/405). The total survival rate in the setting of euploid cystic hygroma without structural abnormality was 84% (108/129). <b><i>Conclusions:</i></b> Counseling regarding outcomes in the setting of first-trimester septated cystic hygroma initially focuses on the strong likelihood of an abnormal karyotype, which occurs in 61% of cases. However, once fetal chromosomal abnormality is excluded, our results demonstrate only a 13% incidence of major structural fetal abnormality, which appears significantly less than previously reported. Normal fetuses have a 77% survival rate. These data represent the largest single-center study of first-trimester cystic hygroma with complete outcome data and therefore will be useful for contemporary patient counseling. Such counseling can be more positive than previously expected, once chromosomal abnormality is first excluded.

Analysis of Genomic Copy Number Variation in Miscarriages During Early and Middle Pregnancy

The purpose of this study was to explore the copy number variations (CNVs) associated with miscarriage during early and middle pregnancy and provide useful genetic guidance for pregnancy and prenatal diagnosis. A total of 505 fetal specimens were collected and CNV sequencing (CNV-seq) analysis was performed to determine the types and clinical significance of CNVs, and relevant medical records were collected. The chromosomal abnormality rate was 54.3% (274/505), among which the numerical chromosomal abnormality rate was 40.0% (202/505) and structural chromosomal abnormality rate was 14.3% (72/505). Chromosomal monosomy mainly occurred on sex chromosomes, and chromosomal trisomy mainly occurred on chromosomes 16, 22, 21, 15, 13, and 9. The incidence of numerical chromosomal abnormalities in ≥35 year-old age pregnant women was significantly higher than &lt;35 year-old age group. The highest incidence of pathogenic CNV (pCNV) was found in fetuses at ≤6 weeks of pregnancy (5.26%), and the incidence of variants of unknown significance (VOUS) CNVs decreased gradually with the increase of gestational age. The rate of chromosomal abnormalities of fetuses in early pregnancy (59.5%) was higher than that of fetuses in middle pregnancy (27.2%) (p &lt; 0.001). There were 168 genes in VOUS + pCNV regions. 41 functions and 12 pathways (p &lt; 0.05) were enriched of these genes by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Some meaningful genetic etiology information such as genes and pathways has been obtained, it may provide useful genetic guidance for pregnancy and prenatal diagnosis.

The Unique Existence of Chromosomal Abnormality in Polyploidy Plants

It is commonly acknowledged that chromosomal abnormality is the popular natural phenomenon especially with polyploidy plants. The unique existence in plants has actually become one of major forces for speciation and evolution. This means that plants existing chromosomal abnormality developing through sexual and asexual pathways shed light on increasing biomass, adapting ecology so these benefits are more important and worth exploring. With regard to the former, chromosomal abnormality plants lead to not only gigantic effect but also increasing phytochemical compounds. As far as ecological perspectives are concerned, this abnormality enhances biotic and abiotic tolerance to adapt to climate change. These things also answer a question why plants can commonly exist with many kinds of chromosomal abnormalities. Based on aforementioned benefits, this review provides human beings with several chances when they need in developing the food security strategies.