Disease relevance of Situs Inversus

• To assess the role of DNAH11, which maps on chromosome 7p21, we searched for mutations in the 82 exons of this gene in a patient with situs inversus totalis, and probable Kartagener syndrome associated with paternal uniparental disomy of chromosome 7 (patUPD7) [1].
• Pol lambda(-/-) mice also show situs inversus totalis and chronic suppurative sinusitis [2].
• We have characterized an insertional mutation in a mouse axonemal dynein heavy chain gene (Mdnah5) that reproduces most of the classical features of PCD, including recurrent respiratory infections, situs inversus and ciliary immotility [3].
• Hydrocephalus, situs inversus, chronic sinusitis, and male infertility in DNA polymerase lambda-deficient mice: possible implication for the pathogenesis of immotile cilia syndrome [2].
• Cilia, as motile and sensory organelles, have been implicated in normal development, as well as diseases including cystic kidney disease, hydrocephalus and situs inversus [4].

High impact information on Situs Inversus

• Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus [5].
• The frameshift allele is also associated with situs inversus among some heterozygous females, suggesting that ZIC3 functions in the earliest stages of LR-axis formation [6].
• The inv (inversion of embryonic turning) mutation in mice was created previously by random insertional mutagenesis; it produces both a constant reversal of left/right polarity (situs inversus) and cyst formation in the kidneys [7].
• We conclude that mutations in the coding region of DNAH11 account for situs inversus totalis and probably a minority of cases of PCD [1].
• Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome) [8].

Chemical compound and disease context of Situs Inversus

• Phenylephrine treatment resulted in a dose-dependent increase of situs inversus with a maximum incidence of 52% [9].
• We report here that the left and right precardiac fields of chick differ in their sensitivity to retinoic acid (RA); while RA applied to the right precardiac field at gastrulation randomizes heart looping, left side treatment induces situs inversus only at high RA concentrations [10].
• Furthermore, calphostin C did not block phenylephrine-induced situs inversus [11].
• Prazosin, an alpha-1 adrenergic antagonist, inhibited phenylephrine-induced situs inversus in a dose-dependent manner [12].
• A23187, a Ca2+ ionophore, induced situs inversus; nifedipine, a L-type Ca2+ channel blocker, partially blocked phenylephrine-induced situs inversus [11].

Biological context of Situs Inversus

• It was evident for many years that patients with trisomy 21 present certain congenital heart defects (atrioventricular canal, ventricular septal defect, tetralogy of Fallot) and seem to be "protected" from others (situs inversus and situs ambiguus, ventricular inversion, transposition of the great arteries) [13].
• METHODS: In a genome-wide search for PCD loci performed in 52 KS families and in 18 PCD families with no situs inversus present (CDO, ciliary dysfunction-only), the maximal pairwise LOD score of 3.36 with D15S205 in the KS families indicated linkage of a KS locus to the long arm of chromosome 15 [14].

Anatomical context of Situs Inversus

• A left-sided superior vena cava draining directly to a left atrium in three patients, or left side of a common atrium in two patients with atrial situs inversus, was identified by the immediate opacification of the left-sided chamber following injection from the left arm [15].
• The control of asymmetry in visceral development appears to be random in the legless mutant; that is, 50% develop normally (situs solitus) and 50% develop with inverted viscera (situs inversus) [16].
• Left preureteral vena cava (retrocaval or circumcaval ureter) associated with partial situs inversus [17].
• The unusual occurrence of situs inversus totalis, ventricular septal defect, hypertrophic subaortic and subpulmonic stenosis, and single coronary artery in a 38-year-old man is presented [18].
• The polysplenia syndrome is the association of multiple spleens, situs inversus, congenital heart disease, and azygous continuation of the inferior vena cava [19].

Gene context of Situs Inversus

• Finally, this study demonstrates a link between ciliary function and situs determination, since compound mutation heterozygosity in DNAI1 results in PCD with situs solitus or situs inversus (KS) [8].
• Infantile nephronophthisis is associated with cystic kidneys, situs inversus, and INVS mutations [20].
• Here we identify the conserved type ID unconventional myosin 31DF gene (Myo31DF) as a unique situs inversus locus in Drosophila [21].
• These results indicate that alpha 1 adrenergic stimulation-induced situs inversus is mediated by the alpha 1A adrenergic receptor subtype and that activation of CaM kinase II but not PKC may be involved [11].
• We have investigated the expression of left/right (L/R) asymmetry markers, nodal and lefty, in the situs inversus mouse mutant Fused toes (Ft) [22].

Analytical, diagnostic and therapeutic context of Situs Inversus

• Right varicocele associated with inferior vena cava malformation in situs inversus: percutaneous treatment with retrograde sclerotherapy [23].
• Radiofrequency catheter ablation of a coronary sinus-ventricular accessory connection in dextrocardia with complete situs inversus and an anomalous inferior vena cava [24].
• We report a case of hepatocellular carcinoma with situs inversus totalis treated by hepatectomy [25].

References