Hereditary breast and ovarian cancer in Andalusian families: a genetic population study.

BACKGROUND: The BRCA1/2 mutation profile varies in Spain according to the geographical area studied. The mutational profile of BRCA1/2 in families at risk for hereditary breast and ovarian cancer has not so far been reported in Andalusia (southern Spain). METHODS: We analysed BRCA1/2 germline mutations in 562 high-risk cases with breast and/or ovarian cancer from Andalusian families from 2010 to 2015. RESULTS: Among the 562 cases, 120 (21.4%) carried a germline pathogenic mutation in BRCA1/2; 50 in BRCA1 (41.7%) and 70 in BRCA2 (58.3%). We detected 67 distinct mutations (29 in BRCA1 and 38 in BRCA2), of which 3 in BRCA1 (c.845C > A, c.1222_1223delAC, c.2527delA) and 5 in BRCA2 (c.293 T > G, c.5558_5559delGT, c.6034delT, c.6650_6654delAAGAT, c.6652delG) had not been previously described. The most frequent mutations in BRCA1 were c.5078_5080delCTG (10%) and c.5123C > A (10%), and in BRCA2 they were c.9018C > A (14%) and c.5720_5723delCTCT (8%). We identified 5 variants of unknown significance (VUS), all in BRCA2 (c.5836 T > C, c.6323G > T, c.9501 + 3A > T, c.8022_8030delGATAATGGA, c.10186A > C). We detected 76 polymorphisms (31 in BRCA1, 45 in BRCA2) not associated with breast cancer risk. CONCLUSIONS: This is the first study reporting the mutational profile of BRCA1/2 in Andalusia. We identified 21.4% of patients harbouring BRCA1/2 mutations, 58.3% of them in BRCA2. We also characterized the clinical data, mutational profile, VUS and haplotype profile.

Structural and functional characterizations of the C-terminal domains of CzcD proteins.

Zinc is a potent antimicrobial component of the innate immune response at the host-pathogen interface. Bacteria subvert or resist host zinc insults by metal efflux pathways that include cation diffusion facilitator (CDF) proteins. The structural and functional examination of this protein class has been limited, with only the structures of the zinc transporter YiiP proteins from E. coli and Shewanella oneidensis described to date. Here, we determine the metal binding properties, solution quaternary structures and three dimensional architectures of the C-terminal domains of the metal transporter CzcD proteins from Cupriavidus metallidurans, Pseudomonas aeruginosa and Thermotoga maritima. We reveal significant diversity in the metal-binding properties and structures of these proteins and discover a potential novel mechanism for metal-promoted dimerization for the Cupriavidus metallidurans and Pseudomonas aeruginosa proteins.