Abnormal childhood phenotypes associated with the same balanced chromosome rearrangements as in the parents

Summary Three patients have been detected because of abnormal phenotypes. Balanced chromosome rearrangements were found in their karyotypes, and in one of the parents in each case.In these three families the association of an abnormal phenotype and a balanced chromosome rearrangement may either be a chance happening or be induced by a submicroscopic loss of chromosome material, for which different position effects may be responsible, according to the case in question.These observations prompt us to ask what decision should be made relative to termination of pregnancy if such a rearrangement is found in amniotic cells in a family with a previous abnormal child.Attachée de recherche à l'I.N.S.E.R.M.Attachée de recherche au C.N.R.S.     

Physical mapping of microdeletions of the chromosome 17 short arm associated with Smith-Magenis syndrome

We used probes from the juxtacentromeric region of the chromosome 17 short arm to map three microdeletions in patients with Smith-Magenis syndrome. The commonclinical findings were: speech delay with behavioural problems associated with broad flat midface, brachycephaly, broad nasal bridge and brachydactyly. We demonstrated, using Southern blot analysis (loss of heterozygosity and gene dosage), that all patients were deleted for two p11.2 markers: pYNM 67-R5 (D17S29) and pA10-41 (D17S71). We determined that one breakpoint was located between D17S58 and D17S29 and the other breakpoint distal to D17S71. The possibility that an unstable region, located between the Smith-Magenis syndrome locus and CMT1A a closely located locus, could be involved in the rearrangements associated with these two inherited diseases is discussed.     

Sesquiterpenes from aerial parts of Ferula vesceritensis

From the dichloromethane extract of aerial parts of Ferula vesceritensis (Apiaceae), 11 sesquiterpene derivatives were isolated. Among them five were compounds designated as 10-hydroxylancerodiol-6-anisate, 2,10-diacetyl-8-hydroxyferutriol-6-anisate, 10-hydroxylancerodiol-6-benzoate, vesceritenone and epoxy-vesceritenol. The six known compounds were identified as feselol, farnesiferol A, lapidol, 2-acetyl-jaeschkeanadiol-6-anisate, lasidiol-10-anisate and 10-oxo-jaesckeanadiol-6-anisate. All the structures were determined by extensive spectroscopic studies including 1D and 2D NMR experiments and mass spectroscopy analysis. Two of the compounds, the sesquiterpene coumarins farnesiferol A and feselol, bound to the model recombinant nucleotide-binding site of an MDR-like efflux pump from the enteropathogenic protozoan Cryptosporidium parvum.     

Thrombin interaction with platelet membrane glycoprotein Ib alpha

The interaction of thrombin with platelet glycoprotein Ibalpha (GPIb alpha) is required for optimal platelet activation. The crystal structures of platelet GPIb alpha bound to thrombin reported by Dumas et al. and Celikel et al. both reveal the simultaneous interaction of GPIb alpha with thrombin exosites I and II but differ markedly regarding how the two proteins interact. The possible consequences on thrombus formation of thrombin interacting with GPIb alpha are discussed in light of these new data.     

Proximity of the CTLA-1 serine esterase and Tcr α loci in mouse and man

The serine esterase CTLA-1 gene was shown by in situ hybridization to map to the D segment of mouse chromosome 14, the same localization as a member of the immunoglobulin super family, Tcr . To further demonstrate the proximity of CTLA-1 and Tcr , genetic linkage was tested in mouse using restriction fragment length polymorphisms and a backcross progeny, and no recombination was observed in the 100 backcross products studied. Recombination events between Tcr /CTLA-1 and the markers Gdh-X and NP-1 show that the most probable order of these loci in the mouse 14D region is NP-1-Tcr /Ctla-1-Gdh-X. In man, the human homologue of CTLA-1 was shown by in situ hybridization to map on chromosome 14, at 14q11-q12, where Tcr also maps. Using the human cell line SUP-Tl, bearing the inversion inv(14)(q11;q32), we further demonstrated the loci order in man to be centromere-NP-1-Tcr -CTLA-1. To complement the cytogenetic and genetic mapping data, we tried to determine the physical distance between the two genes by pulsed field gel electrophoresis (PFGE). DNA prepared from various cell types, both mouse and human, were digested with a panel of rare cutter enzymes and hybridized first with CTLA-1, then with Tcr probes. None of the bands identified hybridized with both Tcr and CTLA-1 probes for either mouse or human cells. Although the physical mapping by PFGE is inconclusive, the cytogenetic and genetic data support close linkage of the Tcr and CTLA-1 genes in both mouse and man, suggesting homology between the D region of mouse chromosome 14 and the q11–q12 region of human chromosome 14, encompassing the Tcr and CTLA-1 loci. These findings also provide another example of proximity of genes coding for a member of the Ig super-family and a serine esterase.     

Colocalization of the genes coding for the α3 and β3 subunits of soluble guanylyl cyclase to human chromosome 4 at q31.3–q33

We have determined the chromosomal location of the human genes coding for the ₃ and ₃ subunits of soluble guanylyl cyclase (GC-S). The study was performed by in situ hybridization of human metaphase spreads with two human cDNA probes, containing the coding sequences of the GC-S ₃ and ₃ subunits, respectively. Each probe gave a strong specific signal on chromosome 4 at the 4q31.3–4q33 region, with the maximal signal in the 4q32 band. The colocalization of both genes in 4q32 represents an interesting feature for the coordinated regulation of expression of both GC-S subunits.     

Chemical investigation of different extracts and essential oil from the tubers of (Tunisian)Cyperus rotundus. Correlation with their antiradical and antimutagenic properties

The mutagenic potential of aqueous, Total Oligomers Flavonoids (TOF), ethyl acetate, and methanol extracts as well as essential oil (EO) obtained from tubers ofCyperus rotundus L. was assessed by “Ames assay”, usingSalmonella tester strains TA98 and TA100, and “SOS chromotest” usingEscherichia coli PQ37 strain with and without an exogenous metabolic activation system (S9). None of the different extracts showed a mutagenic effect. Likewise, the antimutagenicity of the same extracts was tested using the “Ames test” and the “SOS chromotest”. Our results showed thatC. rotundus extracts have antimutagenic effects withSalmonella typhimurium TA98 and TA100 strains towards the mutagen Aflatoxin B1 (AFB1), as well as withE. coli PQ37 strain against AFB1 and nifuroxazide mutagens. A free radical scavenging test was used in order to explore the antioxidant capacity of the extracts obtained from the tubers ofC. rotundus. TOF, ethyl acetate and methanol extracts showed an important free radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical. These extracts showed IC50 values of respectively 5, 20 and 65 μg/ml. The beneficial effects of TOF, ethyl acetate, methanol and essential oil extracts ofC. rotundus have been assessed by antioxidant and antimutagenic activities.