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Background: About 20% of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions. In some populations, especially if relatively isolated, a few number of recurrent mutations is reported, sometimes caused by founder effect. Methods: BRCA1 and BRCA2 screening for mutations was carried out on 1114 breast and/or ovarian cancer patients complying with the eligibility criteria for BRCA testing. Haplotype analysis was performed on the probands carrying recurrent mutations and their relatives, using two sets of microsatellite markers covering the BRCA1 (D17S588, D17S806, D17S902, D17S1325, D17S855, D17S1328, D17S800, and D17S250) and BRCA2 (D13S220, D13S267, D13S171, D13S1701, D13S1698, D13S260, D13S290, D13S1246) loci. The DMLE + 2.2 software was used to estimate the age of BRCA1 c.676delT and BRCA2 c.7806-2A > G. A multiplex PCR and two different primer extension assays were optimized and used for genotyping the recurrent mutations of the two genes. Results: In the time frame of almost 20 years of genetic testing, we have found that five BRCA1 and three BRCA2 mutations are recurrent in a substantial subset of carriers from North-East Italy and neighboring Istria, where they represent more than 50% of all mutations. Microsatellite analyses identified a common haplotype of different length for each mutation. Age estimation of BRCA1 c.676delT and BRCA2 c.7806-2A > G mutations revealed that they arose in the Friuli Venezia Giulia area about 86 and 94 generations ago, respectively. Suggestion of an association between BRCA2 c.7806-2A > G and risk of breast cancer in males has emerged. Finally, we developed a simple and efficient pre-screeening test, performing an in-house primer extension SNaPshot® assay for the rapid identification of the eight recurrent mutations. Conclusions: Proofs of common ancestry has been obtained for the eight recurrent mutations. The observed genotype-phenotype correlation and the proposed rapid mutation detection strategy could improve the clinical management of breast and ovarian patients in North-East of Italy and neighboring geographic areas. [ABSTRACT FROM AUTHOR]

Background: IgA nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition that leads to mesangial proliferation and chronic glomerular inflammation. Analyses of serum IgA1 from IgAN patients revealed an abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may be a result of altered activity of core 1 beta1,3-galactosyltransferase (C1GalT1). To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case control study on cohorts from the Italian population., Methods: We sequenced C1GalT1 coding and promoter regions in 284 IgAN patients and 210 healthy controls. The functional role of 3' untranslated region (3'UTR) SNPs was studied using electrophoretic mobility shift assays and real-time quantitative PCR., Results: We analyzed 8 SNPs in the C1GalT1 gene: 5 SNPs were in the promoter region and 3 SNPs in the 3'UTR. The allele 1365G in the 3'UTR was significantly more frequent in IgAN patients than in healthy controls., Conclusion: The 1365G allele and 1365G/G genotype seem to confer susceptibility to IgAN.