A novel BRCA2 in frame deletion in a Tunisian woman with early onset sporadic breast cancer.

BACKGROUND: Breast cancer is increasing among young women in Tunisia. Germline mutations in the BRCA1/2 genes are associated with a high risk for breast cancer development. However, the true contribution of BRCA1/2 mutation in sporadic breast cancer is not well documented. Our aim is to identify the BRCA2 mutation spectrum in Tunisian young women with breast cancer. METHODS: Screening the BRCA2 gene was performed using DHPLC, DNA sequencing and PCR-RFLP. RESULTS: We identified, in a woman diagnosed with early onset breast cancer, and without family history, a novel in frame deletion 5456delGTAGCA in the exon 11 of the BRCA2 gene which causes a loss of two residues Ser1743-Ser1744. The absence of this deletion in the patients' parents suggests that it is a de novo variant. Furthermore, we screened 108 sporadic cases, 50 familial cases, and 60 controls for the identified del6bp using PCR-RFLP. None of them carried this deletion suggesting that this variant is not a benign polymorphism and probably rare in our population. With regards to the position of the Ser1743-1744 in the BRCT domain, sequence alignment revealed that the Ser1743 is conserved among several species, which may reflect its importance in the BRCA2 function. A modeling of the wild-type and mutated BRC5-BRC6 domain revealed that the deletion of the 2 Serine residues might affect the structure of this BRCA2 domain. CONCLUSIONS: A novel in frame deletion 5456del6bp in BRCA2 gene was identified in an early onset woman with breast cancer and without family history.

Investigation into the artificial ageing effects on the microstructure of an industrial solid waste treated with cement.

Metal hydroxide sludges are classified as hazardous wastes in the European Hazardous Waste Catalogue (EHWC) because of their high heavy metal contents (Zn, Cr, Fe, Cu, etc.) and the release of these pollutants to the environment. Thereby, the disposal of this waste without any treatment is a substantial environmental problem. Stabilization/solidification technologies are widely used for the treatment of wastes and residues in order to obtain inert materials. This work aims to assess the effectiveness of the chemical fixation and solidification of a metal hydroxide sludge generated by the electrotyping surface treatment industry, using Portland Artificial Cement. In order to predict the medium- and long-term behaviour of the solidified waste, an artificial ageing by means of thermal shocks and humidity variation cycles was applied. Scanning Electron Microscopy (SEM) and X-ray Diffraction studies revealed a considerable increase in calcite within the solid matrix after the artificial ageing, which can be attributed to the phenomenon of carbonation. It was also found that the mechanical properties of the solidified material, after ageing, were improved by up to 30%.

The effects of artificial ageing on the leaching behaviour of heavy metals in stabilized/solidified industrial sludge.

The use of a hydraulic binder for the treatment of mineral-based industrial wastes, containing heavy metals, by the chemical fixation and solidification (CFS) technique has raised serious questions regarding the prediction of the behaviour of these pollutants in the obtained solid matrix. It seems necessary, for this reason, to study the behaviour of these metals in response to leaching in order to evaluate their chemical speciation within the solidified sludge over the medium and long-terms. Within the framework of the current research, we applied the CFS technique to metallic hydroxide sludge, produced by the electrotyping surface treatment industry, by using Portland artificial cement (PAC). Compaction at the paste phase of this treated sludge resulted in up to 35% enhancement of the retention of pollutants, mainly trivalent chromium, in a cementing matrix, as compared with the classical technique that uses a simple vibration of sludge at the paste phase. The implemented process led to an improvement in the compactness of the sludge, and thus assured a better retention of heavy metals in response to the leaching of this treated sludge. The evaluation of the chemical properties of the materials obtained after an artificial ageing process using humidity variation cycles and thermal chocks also revealed a significant improvement in the retention capacity of heavy metals in the solidified sludge, which was mainly favoured by the development of carbonation. In fact, the release of the heavy metals from the above mentioned treated sludge was reduced by 58% for zinc and 51% for trivalent chromium after the artificial ageing process.

[Fabry's disease with isolated disease of the cardiac muscle, manifesting as hypertrophic cardiomyopathy]. / Fabryho nemoc s izolovaným postizením srdecní svaloviny, probíhající pod obrazem hypertrofické kardiomyopatie.

A case is presented of Fabry's disease manifesting in an adult (aged 64) as hypertrophic nonobstructive cardiomyopathy caused by massive ceramidtrihexoside storage confined exclusively to the cardiocytes. There was no storage detectable in capillaries or in any other structure of the organs examined (liver, pancreas, brain, aorta, pulmonary artery, coronary arteries, heart valves). The clinical picture was dominated by heart failure slowly progressing during the last fifteen years of the patient's life terminated by pulmonary thromboembolism. There were no clinical signs of ocular, renal or skin affection. Since no unfixed tissues were available for enzyme analysis diagnosis had to be done using formaldehyde fixed tissues. The isolated stored lipid was characterized by TLC and by proton magnetic resonance analysis as globotriaosyl ceramide (Gal alpha 1-4 Gal beta 1-4 Glc beta 1-1' Cer) and was proved to be cleaved by control cell homogenates but left intact by those prepared from Fabry mutant cells (leukocytes, cultured fibroblasts). alpha galactosidase activity in each of his four daughters was in heterozygous range (peripheral leukocytes were used for analysis). The existing variants of cardiological syndromes in Fabry's disease are reviewed together with problems of diagnosis of atypical cases.