Cr(1/3)Zr2P3O12 with unusual tetrahedral coordination of Cr(III): peculiarities of the formation, thermal stability and application as a pigment.

All the known chromium(III) NASICON-related phosphates are considered to be solid solutions. In these compounds chromium atoms share their position in the basic framework of the crystal lattice with other structure forming elements such as zirconium. In our study, we have hypothesised a completely new way of structural organisation of the chromium(III) zirconium(IV) NASICON framework, consisting in the distribution of chromium over the charge-compensating atom sites with tetrahedral oxygen coordination. The possibility of formation of the corresponding phosphate, Cr(1/3)Zr2P3O12, was studied using a classical ceramic route and a sol-gel method. Structural affiliation of the obtained pure phase product was studied using XRD analysis. The results confirmed that the Cr(1/3)Zr2P3O12 phosphate belongs to monoclinic SW-subtype of the NASICON family. In this structure, chromium atoms occupy charge-compensating sites with a strongly distorted tetrahedral oxygen environment. To the best of our knowledge, it is the first example of tetrahedral coordination of chromium(III) in phosphates. Along with the unusual crystallographic characteristics of chromium, special attention in this paper is devoted to the thermal stability of this phosphate and to its performance as an inorganic pigment. The sample was characterised by heating microscopy and DTA study, particle size distribution analysis, and IR- and VIS-spectroscopy. The stability of the obtained powder in a glaze environment, its colouring performance and lightfastness are discussed as well.

Spectrum and characterisation of BRCA1 and BRCA2 deleterious mutations in high-risk Czech patients with breast and/or ovarian cancer.

BACKGROUND: The incidence of breast cancer has doubled over the past 20 years in the Czech Republic. Hereditary factors may be a cause of young onset, bilateral breast or ovarian cancer, and familial accumulation of the disease. BRCA1 and BRCA2 mutations account for an important fraction of hereditary breast and ovarian cancer cases. One thousand and ten unrelated high-risk probands with breast and/or ovarian cancer were analysed for the presence of a BRCA1 or BRCA2 gene mutation at the Masaryk Memorial Cancer Institute (Czech Republic) during 1999-2006. METHODS: The complete coding sequences and splice sites of both genes were screened, and the presence of large intragenic rearrangements in BRCA1 was verified. Putative splice-site variants were analysed at the cDNA level for their potential to alter mRNA splicing. RESULTS: In 294 unrelated families (29.1% of the 1,010 probands) pathogenic mutations were identified, with 44 different BRCA1 mutations and 41 different BRCA2 mutations being detected in 204 and 90 unrelated families, respectively. In total, three BRCA1 founder mutations (c.5266dupC; c.3700_3704del5; p.Cys61Gly) and two BRCA2 founder mutations (c.7913_7917del5; c.8537_8538del2) represent 52% of all detected mutations in Czech high-risk probands. Nine putative splice-site variants were evaluated at the cDNA level. Three splice-site variants in BRCA1 (c.302-3C>G; c.4185G>A and c.4675+1G>A) and six splice-site variants in BRCA2 (c.475G>A; c.476-2>G; c.7007G>A; c.8755-1G>A; c.9117+2T>A and c.9118-2A>G) were demonstrated to result in aberrant transcripts and are considered as deleterious mutations. CONCLUSION: This study represents an evaluation of deleterious genetic variants in the BRCA1 and 2 genes in the Czech population. The classification of several splice-site variants as true pathogenic mutations may prove useful for genetic counselling of families with high risk of breast and ovarian cancer.

High occurrence of BRCA1 intragenic rearrangements in hereditary breast and ovarian cancer syndrome in the Czech Republic.

BACKGROUND: Alterations in the highly penetrant cancer susceptibility gene BRCA1 are responsible for the majority of hereditary breast and/or ovarian cancers. However, the number of detected germline mutations has been lower than expected based upon genetic linkage data. Undetected deleterious mutations in the BRCA1 gene in some high-risk families could be due to the presence of intragenic rearrangements as deletions, duplications or insertions spanning whole exons. Standard PCR-based screening methods are mainly focused on detecting point mutations and small insertions/deletions, but large rearrangements might escape detection.The purpose of this study was to determine the type and frequency of large genomic rearrangements in the BRCA1 gene in hereditary breast and ovarian cancer cases in the Czech Republic. METHODS: Multiplex ligation-dependent probe amplification (MLPA) was used to examine BRCA1 rearrangements in 172 unrelated patients with hereditary breast and/or ovarian cancer syndrome without finding deleterious mutation after complete screening of whole coding regions of BRCA1/2 genes. Positive MLPA results were confirmed and located by long-range PCR. The breakpoints of detected rearrangements were characterized by sequencing. RESULTS: Six different large deletions in the BRCA1 gene were identified in 10 out of 172 unrelated high-risk patients: exons 1A/1B and 2 deletion; partial deletion of exon 11 and exon 12; exons 18 and 19 deletion; exon 20 deletion; exons 21 and 22 deletion; and deletion of exons 5 to 14. The breakpoint junctions were localized and further characterized. Destabilization and global unfolding of the mutated BRCT domains explain the molecular and genetic defects associated with the exon 20 in-frame deletion and the exon 21 and 22 in-frame deletion, respectively. CONCLUSION: Using MLPA, mutations were detected in 6% of high-risk patients previously designated as BRCA1/2 mutation-negative. The breakpoints of five out of six large deletions detected in Czech patients are novel. Screening for large genomic rearrangements in the BRCA1 gene in the Czech high-risk patients is highly supported by this study.