Genetic basis of human left–right asymmetry disorders

2014 ◽  
Vol 16 ◽  
Author(s):  
Hao Deng ◽  
Hong Xia ◽  
Sheng Deng
Keyword(s):  
Situs Inversus ◽  
Genetic Basis ◽  
Chromosomal Abnormalities ◽  
The Body ◽  
Disease Genes ◽  
Internal Organs ◽  
Abdominal Organs ◽  
Pathogenic Genes ◽  
Left Right Asymmetry ◽  
Reduced Penetrance

Humans and other vertebrates exhibit left–right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, includingsitus inversusandheterotaxy.Situs inversusis complete mirror-imaged arrangement of the internal organs along LR axis, whereasheterotaxyis abnormal arrangement of the internal thoraco-abdominal organs across LR axis of the body, most of which are associated with complex cardiovascular malformations. Both disorders are genetically heterogeneous with reduced penetrance, presumably because of monogenic, polygenic or multifactorial causes. Research in genetics of LR asymmetry disorders has been extremely prolific over the past 17 years, and a series of loci and disease genes involved insitus inversusandheterotaxyhave been described. The review highlights the classification, chromosomal abnormalities, pathogenic genes and the possible mechanism of human LR asymmetry disorders.

Situs Inversus Totalis

2001 ◽  
Vol 20 (1) ◽  
pp. 63-67 ◽  
Author(s):  
Janie Spoon
Keyword(s):  
Situs Inversus ◽  
Vena Cava ◽  
Situs Inversus Totalis ◽  
Mirror Image ◽  
The Body ◽  
Radiographic Examination ◽  
Internal Organs ◽  
Radiographic Findings ◽  
Situs Solitus ◽  
The Right

EXTERNALLY, THE HUMAN BODY appears symmetric; if a line is drawn down the middle of the body, each side appears identical. However, this is not true of the internal anatomy. For example, there is one heart, which lies in the left chest, one liver, in the right abdomen, and one stomach, in the left abdomen. The term situs refers to the position or location of an organ, specifically, the position of the atria and abdominal viscera in relation to the midline of the body.1 There are three types of situs: solitus, inversus, and ambiguous. Situs solitus refers to the normal arrangement of organs, with the right atrium, liver, gallbladder, trilobed lung, and inferior vena cava on the right side and the left atrium, stomach, spleen, bilobed lung, and descending aorta on the left side (Figures 1–3). Situs inversus totalis refers to a mirror image reversal of the normal position of the internal organs (Figures 4 and 5). 1 The incidence of situs inversus totalis is 1 in every 8,000 to 25,000 births, and the condition is most often diagnosed by radiographic examination.2Situs ambiguous, often referred to as heterotaxia, is the random arrangement of the internal organs and is associated with splenic abnormalities and congenital heart disease.3 The purpose of this column is to discuss the embryology, pathophysiology, and diagnosis of situs inversus totalis and to review a case study with radiographic findings.

scholarly journals MNS1 variant associated with situs inversus and male infertility

2019 ◽  
Vol 28 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Joseph S. Leslie ◽  
Lettie E. Rawlins ◽  
Barry A. Chioza ◽  
Oluwaseun R. Olubodun ◽  
Claire G. Salter ◽  
...  
Keyword(s):  
Male Infertility ◽  
Situs Inversus ◽  
Autosomal Recessive ◽  
Internal Organs ◽  
Genome Wide ◽  
Whole Exome ◽  
Snp Mapping ◽  
Left Right Asymmetry ◽  
And Function ◽  
Laterality Defects

Abstract Ciliopathy disorders due to abnormalities of motile cilia encompass a range of autosomal recessive conditions typified by chronic otosinopulmonary disease, infertility, situs abnormalities and hydrocephalus. Using a combination of genome-wide SNP mapping and whole exome sequencing (WES), we investigated the genetic cause of a form of situs inversus (SI) and male infertility present in multiple individuals in an extended Amish family, assuming that an autosomal recessive founder variant was responsible. This identified a single shared (2.34 Mb) region of autozygosity on chromosome 15q21.3 as the likely disease locus, in which we identified a single candidate biallelic frameshift variant in MNS1 [NM_018365.2: c.407_410del; p.(Glu136Glyfs*16)]. Genotyping of multiple family members identified randomisation of the laterality defects in other homozygous individuals, with all wild type or MNS1 c.407_410del heterozygous carriers being unaffected, consistent with an autosomal recessive mode of inheritance. This study identifies an MNS1 variant as a cause of laterality defects and male infertility in humans, mirroring findings in Mns1-deficient mice which also display male infertility and randomisation of left–right asymmetry of internal organs, confirming a crucial role for MNS1 in nodal cilia and sperm flagella formation and function.

Dosage requirement of Pitx2 for development of multiple organs

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4643-4651 ◽  
Author(s):  
P.J. Gage ◽  
H. Suh ◽  
S.A. Camper
Keyword(s):  
Heart Development ◽  
Threshold Level ◽  
The Body ◽  
Null Alleles ◽  
Allelic Series ◽  
Heart Tube ◽  
Rieger Syndrome ◽  
Multiple Organs ◽  
Abdominal Organs ◽  
Left Right Asymmetry

Pitx2 is a homeodomain transcription factor that is mutated in Rieger syndrome, a haploinsufficiency disorder affecting eyes and teeth. Pitx2 also has a postulated role in left-right axis determination. We assessed the requirements for Pitx2 directly by generating hypomorphic and null alleles. Heterozygotes for either allele have eye abnormalities consistent with Rieger syndrome. The ventral body wall fails to close in embryos homozygous for the null allele, leaving the heart and abdominal organs externalized and the body axis contorted. In homozygotes for either allele, the heart tube undergoes normal, rightward looping and the stomach is positioned normally. In contrast, homozygotes for both alleles exhibit right isomerization of the lungs. Thus, Pitx2 is required for left-right asymmetry of the lungs but not other organs. Homozygotes for either allele exhibit septal and valve defects, and null homozygotes have a single atrium proving that a threshold level of Pitx2 is required for normal heart development. Null homozygotes exhibit arrest of pituitary gland development at the committed Rathke pouch stage and eye defects including optic nerve coloboma and absence of ocular muscles. This allelic series establishes that Pitx2 is required for the development of mulitple organs in a dosage-sensitive manner.

scholarly journals Heterotaxy: fluctuat nec mergitur

2021 ◽  
Vol 31 (7) ◽  
pp. 1200-1201
Author(s):  
Lucile Houyel ◽  
Anne Moreau de Bellaing ◽  
Damien Bonnet
Keyword(s):  
Situs Inversus Totalis ◽  
The Body ◽  
Abdominal Organ ◽  
Heterotaxy Syndrome ◽  
Internal Organs ◽  
Abdominal Organs ◽  
International Pediatric ◽  
Thoracic And Abdominal ◽  
The Relationship ◽  
Visceral Heterotaxy

AbstractThe International Pediatric and Congenital Cardiac Code (IPCCC) states that visceral heterotaxy is defined as “a congenital malformation in which the internal thoraco-abdominal organs demonstrate abnormal arrangement across the left-right axis of the body. By convention, in congenital cardiology, heterotaxy syndrome does not include patients with complete mirror-imaged arrangement of the internal organs along the left-right axis also known as “total mirror imagery” or “situs inversus totalis”.” [www.ipccc.net]In patients with heterotaxy, it is important to describe both the cardiac relations and the junctional connections of the cardiac segments, with documentation of the arrangement of the atrial appendages, the ventricular topology, the nature of the unions of the segments across the atrioventricular and the ventriculoarterial junctions, the infundibular morphologies, and the relationships of the arterial trunks in space. Particular attention is required for the venoatrial connections, since these are so often abnormal. The relationship and arrangement of the remaining thoraco-abdominal organs, including the lungs, the spleen, the liver, and the intestines, also must be described separately, because, although common patterns of association have been identified, there are frequent exceptions to these common patterns. Therefore, in patients with heterotaxy, it is important to describe each thoracic and abdominal organ independently.

scholarly journals I. Tables of the weights of the human body and the internal organs in the sane and insane of both sexes at various ages

1862 ◽  
Vol 11 ◽  
pp. 124-126
Keyword(s):  
Old Age ◽  
Human Body ◽  
Left Lung ◽  
Lunatic Asylum ◽  
The Body ◽  
Internal Organs ◽  
Human Organs ◽  
Abdominal Organs ◽  
The Right ◽  
Maximum Minimum

These Tables have been compiled from notes of 2086 examinations made at St. Marylebone Infirmary between 1839 and 1847, and of 528 examinations in cases of insanity made at the Somerset Lunatic Asylum, between 1848 and the end of December 1860, comprehending, in all, a period of twenty-one years. The Tables are submitted with the hope that they may aid in forming a standard of the weight of the human organs at different stages of life from early infancy to old age. The cases are distributed under eighteen periods of life, and the Tables show the height and weight of the body, and the weight of the encephalon and its several parts, the right and left lung, the heart and all the abdominal organs; giving the maximum, minimum and average in each period.

scholarly journals Anesthetic management of a patient with situs inversus posted for laparoscopic cholecystectomy

2017 ◽  
Vol 5 (9) ◽  
pp. 4187 ◽  
Author(s):  
Plabon Hazarika ◽  
Prabir Pranjal Das
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
General Anesthesia ◽  
Situs Inversus ◽  
Anesthetic Management ◽  
Situs Inversus Totalis ◽  
The Body ◽  
North East India ◽  
North East ◽  
First Case ◽  
Left Right Asymmetry

Situs inversus totalis is a rare congenital visceral malrotation anomaly that results from disturbances in establishment of left-right asymmetry. It is an autosomal recessive condition, in which organs are transposed from their normal location to the opposite side of the body and the predicted incidence is one in 10, 000 among the general population. In a patient with situs inversus totalis, not just the diagnosis of any acute abdomen pathology is difficult but equally challenging is the anesthetic management during the respective surgical procedure. We are reporting a patient who had situs inversus totalis and was operated for laparoscopic cholecystectomy under general anesthesia, and endotracheal tube as an airway conduit. Though the problems related to such patients are mainly of surgical feasibility, an anesthesiologist must be aware of the associated problems of both, situs inversus and the surgical procedures. The present case report lays an emphasis on the potential difficulties during anesthetic management and its various implications in a remote area in North East India with resource limitations. To the best of our knowledge, we report the first case from a remote are in North East India of a successful laparoscopic cholecystectomy in a patient with situs inversus totalis under general anesthesia which was uneventful.

The effectiveness of use of enterosorbent Shelltic Es when rearing of young pigs

2020 ◽  
pp. 3-11
Author(s):  
S. Grikshas ◽  
N. Kulmakova ◽  
K. Spitsyna ◽  
A. Dar’in ◽  
T. Mittelshtein
Keyword(s):  
Average Daily Gain ◽  
Live Weight ◽  
Feed Additives ◽  
The Body ◽  
Control Group ◽  
Internal Organs ◽  
Feed Digestibility ◽  
Young Pigs ◽  
Carcinogenic Effects ◽  
Experimental Group

Mycotoxins have been formed in feed are secondary metabolites of fungi and are quite stable substances that have teratogenic, mutagenic and carcinogenic effects. An effective way to combat mycotoxins in feed is the use of feed additives that adsorb toxins, prevent their absorption in the gastrointestinal tract of the animal and are excreted from the body. The infl uence of coconut enterosorbent Shelltic Es on fattening and meat qualities of young pigs has been studied. It has been found in the process of fattening that the highest feed digestibility was in pigs of the experimental group, in the diet of which enterosorbent has been added. The results of studies of the chemical composition and technological properties of pork have been provided. The positive eff ect of enterosorbent on precocity, absolute average daily gain of live weight and reduction of feed expenditures per 1 kg of gain has been revealed. In pigs from the experimental group the average thickness of the fat was higher and the area of the “muscle eye” was lower compared with animals of the control group, which indicates that higher rates of carcass yield have been obtained due to faster accumulation of fat tissue. The weight of internal organs of pigs indicates the intensity of metabolic processes in the body. In experimental animals the weight of the lungs was 0,1 kg lower, and the liver and heart were higher by 0,13 and 0,01 kg, respectively. Enterosorbent had no effect on the content of vitamins in the liver of pigs of the compared groups. The content of impurities of organochlorine toxicants and toxic elements in the meat and liver of animals of the experimental group was lower than that of control analogues. Therefore, the use of enterosorbent Shelltic Es promotes more active excretion of them from the body.

ACUTE TOXICITY OF CERIUM DIOXIDE NANOPARTICLES

2019 ◽  
pp. 56-62
Author(s):  
N. V. Khodykina ◽  
L. P. Tochilkina ◽  
O. N. Novikova ◽  
M. S. Sroslov ◽  
A. Ya. Pocheptsov ◽  
...  
Keyword(s):  
Toxic Effect ◽  
Cerium Dioxide ◽  
Intraperitoneal Administration ◽  
Body Weight Loss ◽  
The Body ◽  
Prooxidant Effect ◽  
High Exposure ◽  
Abdominal Organs ◽  
Metabolic Imbalance ◽  
Hematological Changes

The resorptive effects of 0.01 M cerium nanodioxide sol upon single intraperitoneal administration to rats have been studied. The acute exposure to nanoparticles was found to have a dose-dependent general toxic effect on the body (weight loss, inflammatory changes in the abdominal organs, modification of individual behavior, hematological changes, metabolic imbalance), which develops on the background of POL activation. The prooxidant effect of cerium dioxide nanoparticles is demonstratively manifested at relatively high exposure levels (80–8 mg / kg). The threshold dose for the general toxic effect (Limch integr) is equal to 0.8 mg / kg.

scholarly journals Ferromagnetic soft catheter robots for minimally invasive bioprinting

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cheng Zhou ◽  
Youzhou Yang ◽  
Jiaxin Wang ◽  
Qingyang Wu ◽  
Zhuozhi Gu ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
The Body ◽  
Magnetic Actuation ◽  
Internal Organs ◽  
Planar Surfaces ◽  
Reinforced Polymer ◽  
Direct Fabrication ◽  
Digitally Controlled

AbstractIn vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication.

Hematological and toxicological evaluation of formaldehyde as a potential cause of human leukemia

2010 ◽  
Vol 30 (7) ◽  
pp. 725-735 ◽  
Author(s):  
Bernard D Goldstein
Keyword(s):  
Bone Marrow ◽  
Chromosomal Abnormalities ◽  
Species Difference ◽  
The Body ◽  
Myelogenous Leukemia ◽  
Laboratory Animals ◽  
Human Leukemia ◽  
Toxicological Evaluation ◽  
Hematopoietic Stem ◽  
Hematological Cancers

Epidemiological findings suggesting that formaldehyde exposure is associated with a higher risk of acute myelogenous leukemia (AML) and other hematological cancers have led to consideration of the potential mechanism of action by which inhalation of this rapidly reactive agent can cause bone marrow cancer. Two major mechanism-based arguments against formaldehyde as a leukemogen have been the difficulty in envisioning how inhaled formaldehyde might penetrate to the bone marrow; and the lack of similarity of non-cancer effects to other known human myeloleukemogens, particularly the absence of pancytopenia in humans or laboratory animals exposed to high levels. However, both of these arguments have been addressed by the recent finding of a pancytopenic effect and chromosomal abnormalities in heavily exposed Chinese workers which, if replicated, are indicative of a genotoxic effect of formaldehyde on hematopoietic stem cells that is in keeping with other known human leukemogens. Review of the body of evidence suggests an apparent discrepancy between studies in laboratory animals, which generally fail to show evidence of penetration of formaldehyde into the blood or evidence of blood or bone marrow genotoxicity, and studies of exposed humans in which there tends to be evidence of genotoxicity in circulating blood cells. One possible explanation for this discrepancy is species difference. Another possible explanation is that myeloid precursors within the nasal mucosa may be the site for leukemogenesis. However, chloromas, which are local collections of myeloid tumor cells, are rarely if ever found in the nose. Other proposed mechanisms for formaldehyde leukemogenesis are reviewed, and dose issues at the interface between the epidemiological and hematotoxicological findings are explored.

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