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Our center has observed a substantial increase in the detection rate of fetal left–right(LR) asymmetry disorders between March and May 2023. This finding has raised concerns because these pregnant women experienced the peak outbreak of SARS-CoV-2 in China during their first trimester. To explore the relationship between maternal SARS-CoV-2 infection and fetal LR asymmetry disorders. A retrospective collection of clinical and ultrasound data diagnosed as fetal LR asymmetry disorders was conducted from January 2018 to December 2023. The case–control study involved fetuses with LR asymmetry disorders and normal fetuses in a 1:1 ratio. We evaluated and compared the clinical and fetal ultrasound findings in pregnant women with SARS-CoV-2 infection and pregnant women without infection. The Student t -test was utilized to compare continuous variables, while the chi-squared test was employed for univariable analyses. The incidence rate of LR asymmetry disorders from 2018 to 2023 was as follows: 0.17‰, 0.63‰, 0.61‰, 0.57‰, 0.59‰, and 3.24‰, respectively. A total of 30 fetuses with LR asymmetry disorders and 30 normal fetuses were included. This case–control study found that SARS-CoV-2 infection (96.67% vs 3.33%, P  = .026) and infection during the first trimester (96.55% vs 3.45%, P  = .008) were identified as risk factors. The odds ratio values were 10.545 (95% CI 1.227, 90.662) and 13.067 (95% CI 1.467, 116.419) respectively. In cases of SARS-CoV-2 infection in the first trimester, the majority of infections (88.1%, 37/42) occurred between 5 and 6 weeks of gestation. We found that 43.7% (66/151) of fetuses with LR asymmetry disorder had associated malformations, 90.9% (60/66) exhibited cardiac malformations. SARS-CoV-2 infection during the first trimester significantly increases the risk of fetal LR asymmetry disorders, particularly when the infection occurs between 5 and 6 gestation weeks. The most common associated malformation is heart malformation.

Background Left–right (LR) asymmetry disorders present a complex etiology, with genetic factors emerging as a primary contributor. This study aims to explore the genetic underpinnings of chromosomal variants and individual genes in fetuses afflicted with prenatal LR asymmetry disorder. Methods Through a retrospective analysis conducted between 2020 and 2023 at Tongji Hospital, Huazhong University of Science and Technology, genetic outcomes of LR asymmetric disorder were scrutinized utilizing copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) methodologies. Results With a combination of CNV-seq and WES, 5 fetuses in 17 patients with LR asymmetry had chromosomal or genetic variants. CNV-seq revealed a 16p11.2 microdeletion syndrome in a situs inversus fetus presenting pathogenic and a 2q36.3 microduplication syndrome in a fetus with Heterotaxy presenting a variant of uncertain significance (VUS). WES identified NM_198075.4:c.755del in the LRRC56 gene and NM_001454.4:c.865_868dup in the FOXJ1 gene in two situs inversus cases, along with two variants in DNAH5 in two other fetuses. Further bioinformatics scrutiny was conducted to assess the protein structure and function prediction of these variants, ultimately indicating their potential pathogenicity. Conclusion The study highlights that fetuses with LR asymmetric disorders may have copy number variants, underscoring the significance of mutations in LRRC56 and FOXJ1 in the development of LR asymmetry disorders.

Situs inversus totalis is a rare congenital abnormality characterized by a mirror-image transposition of both the abdominal and the thoracic organs. While this anomaly is known since the ancient times, practicing doctors do not have much experience with it. Laterality is established early in development, and any failure in that process might lead to a wide variety of disorders which may be partial or complete. describes the normal anatomy, is the complete reversal, and is used for any other abnormality of left-right development. Sidedness is regulated by genes: over 100 genes have been linked to laterality defects. Frequency of situs inversus is 1:10,000 and is more frequent in males: 1.5:1. Advanced imaging modalities can be used to assess fine anatomical details, which play a crucial role in these cases to plan radiologic or surgical interventions. Percutaneous biliary procedures, portal vein embolization are really challenging procedures in SIT patients due to the mirror effect. As most surgeons are right-handed, SIT operations can cause difficulties: handling the instruments with their left hand or the pedals with their left foot can be uncomfortable Organ, especially liver transplantation represents an extraordinary surgical challenge. Solutions to overcome the anatomic differences include the use of segment or reduced size graft with rotation, modified piggy-back technique, side to-side caval anastomosis, and vascular conduit. Because of its rarity and special nature, surgical patients with situs inversus may require more flexibility and creativity from the surgical team.

How left-right patterning drives asymmetric morphogenesis is unclear. Here, we have quantified shape changes during mouse heart looping, from 3D reconstructions by HREM. In combination with cell labelling and computer simulations, we propose a novel model of heart looping. Buckling, when the cardiac tube grows between fixed poles, is modulated by the progressive breakdown of the dorsal mesocardium. We have identified sequential left-right asymmetries at the poles, which bias the buckling in opposite directions, thus leading to a helical shape. Our predictive model is useful to explore the parameter space generating shape variations. The role of the dorsal mesocardium was validated in Shh-/- mutants, which recapitulate heart shape changes expected from a persistent dorsal mesocardium. Our computer and quantitative tools provide novel insight into the mechanism of heart looping and the contribution of different factors, beyond the simple description of looping direction. This is relevant to congenital heart defects. The heart is an organ that pumps blood throughout the body to supply oxygen and to remove carbon dioxide and waste products. Its left and right side are shaped differently to circulate blood through two pathways: to the lungs and to all other organs. As the heart develops inside the embryo, it transforms from a simple, straight tube into a helix shape similar to the shell of a snail. During this process called looping, the helix coils anti-clockwise, which determines where the left and right side of the heart form. It is thought that over 20% of heart anomalies in children may be caused by abnormal looping. Much of what is known about heart development is based on studies in chicken and fish. However, despite its medical significance, it was not fully understood how the heart of mammals acquires its helix shape. Now, Le Garrec et al. were able to investigate the looping process more closely by creating 3D images and computer simulations of the developing mouse heart. First, Le Garrec et al. studied the cells that build the heart and found that left and right cells contribute differently. For example, the number of cells differed between left and right side. The computer simulations then showed that looping is caused by mechanical constraints, which occur because of the way the heart attaches to the body. These mechanical constraints amplify the differences between left and right cells and cause the heart to acquire an oriented helix shape. The computer model could predict how the heart shape will change depending on the type of mechanical constraint, or if cells will have varying levels of left/right differences. The model could also accurately reproduce the shape changes observed in the mouse embryo and predict the abnormal shape of embryos with a genetic defect. The tools generated in this study will help to understand how anomalies could appear as the heart develops in the embryo, and may in the future also be applied to other organs like the gut. A next step will be to explore how genes control the looping of the heart and contribute to heart anomalies in children.

The formation of the embryonic left–right axis is a fundamental process in animals, which subsequently conditions both the shape and the correct positioning of internal organs. During vertebrate early development, a transient structure, known as the left–right organizer, breaks the bilateral symmetry in a manner that is critically dependent on the activity of motile and immotile cilia or asymmetric cell migration. Extensive studies have partially elucidated the molecular pathways that initiate left–right asymmetric patterning and morphogenesis. Wnt/planar cell polarity signaling plays an important role in the biased orientation and rotational motion of motile cilia. The leftward fluid flow generated in the cavity of the left–right organizer is sensed by immotile cilia through complex mechanisms to trigger left-sided calcium signaling and lateralized gene expression pattern. Disrupted asymmetric positioning or impaired structure and function of cilia leads to randomized left–right axis determination, which is closely linked to laterality defects, particularly congenital heart disease. Despite of the formidable progress made in deciphering the critical contribution of cilia to establishing the left–right asymmetry, a strong challenge remains to understand how cilia generate and sense fluid flow to differentially activate gene expression across the left–right axis. This review analyzes mechanisms underlying the asymmetric morphogenesis and function of the left–right organizer in left–right axis formation. It also aims to identify important questions that are open for future investigations.

Situs inversus totalis is a rare congenital abnormality characterized by a mirror-image transposition of both the abdominal and the thoracic organs. While this anomaly is known since the ancient times, practicing doctors do not have much experience with it. Laterality is established early in development, and any failure in that process might lead to a wide variety of disorders which may be partial or complete. Situs solitus describes the normal anatomy, situs inversus is the complete reversal, and situs ambiguous is used for any other abnormality of left-right development. Sidedness is regulated by genes: over 100 genes have been linked to laterality defects. Frequency of situs inversus is 1:10,000 and is more frequent in males: 1.5:1. Advanced imaging modalities can be used to assess fine anatomical details, which play a crucial role in these cases to plan radiologic or surgical interventions. Percutaneous biliary procedures, portal vein embolization are really challenging procedures in SIT patients due to the mirror effect. As most surgeons are right-handed, SIT operations can cause difficulties: handling the instruments with their left hand or the pedals with their left foot can be uncomfortable Organ, especially liver transplantation represents an extraordinary surgical challenge. Solutions to overcome the anatomic differences include the use of segment or reduced size graft with rotation, modified piggy-back technique, side to-side caval anastomosis, and vascular conduit. Because of its rarity and special nature, surgical patients with situs inversus may require more fexibility and creativity from the surgical team. Keywords: situs inversus totalis, left-right asymmetry, mirror-image transposition, kidney transplantation, liver transplantation, organ donation

Joubert syndrome and related diseases (JSRD) are cerebello-oculo-renal syndromes with phenotypes including cerebellar hypoplasia, retinal dystrophy, and nephronophthisis (a cystic kidney disease). Mutations in AHI1 are the most common genetic cause of JSRD, with developmental hindbrain anomalies and retinal degeneration being prominent features. We demonstrate that Ahi1, a WD40 domain-containing protein, is highly conserved throughout evolution and its expression associates with ciliated organisms. In zebrafish ahi1 morphants, the phenotypic spectrum of JSRD is modeled, with embryos showing brain, eye, and ear abnormalities, together with renal cysts and cloacal dilatation. Following ahi1 knockdown in zebrafish, we demonstrate loss of cilia at Kupffer’s vesicle and subsequently defects in cardiac left–right asymmetry. Finally, using siRNA in renal epithelial cells we demonstrate a role for Ahi1 in both ciliogenesis and cell–cell junction formation. These data support a role for Ahi1 in epithelial cell organization and ciliary formation and explain the ciliopathy phenotype of AHI1 mutations in man.