BRCA1 and BRCA2 germline mutations contribute to a significant number of familial and hereditary breast and/or ovarian cancers. The proportion of high-risk families with breast and/or ovarian cancer cases due to mutations in these tumor suppressor genes varies widely among populations. In some population, a wide spectrum of different mutations in both genes are present, whereas in other groups specific mutations in BRCA1 and BRCA2 have been reported with high frequency. Most of these mutations are prevalent in restricted populations as consequence of a founder effect. The comparison of haplotypes between families with the same mutation can distinguish whether high-frequency alleles derive from an older or more recent single mutational event or whether they have arisen independently more than once. Here, we review some of the most well-known and significant examples of founder mutations in BRCA genes found in European and non-European populations. In conclusion, the identification of the ethnic group of families undergoing genetic counseling enables the geneticist and oncologist to make more specific choices, leading to simplify the clinical approach to genetic testing carried out on members of high-risk families. Futhermore, the high frequency of founder mutations, allowing to analyze a large number of cases, might provide accurate information regarding their penetrance.

Background and Purpose-Intra-arterial thrombolysis can be used for treatment of basilar artery occlusion. Predictors of outcome before initiation of treatment are of special interest. Methods-From 1992 to 2010, we treated 106 consecutive patients with basilar artery occlusion with intra-arterial thrombolysis. Baseline characteristics, treatment, clinical course, and 3-month and long-term outcomes (Ն12 months) were assessed. Outcome parameters were vessel recanalization after treatment, complications, modified Rankin scale (mRS) score, and mortality after 3 months and in the long-term. Results-At 3 months, clinical outcome was good (mRS score, 0 -2) in 33.0% of the patients and moderate (mRS score, 3) in 11.3%. Mortality was 40.6%. Partial or complete recanalization was achieved in 69.8% of the patients, and symptomatic intracranial hemorrhage occurred in 1 patient (0.9%). Between 3-month and long-term follow-up, 22 survivors (40.8%) showed clinical improvement of at least 1 point on the mRS score, 29 (53.7%) were functionally unchanged, and 3 (5.7%) showed functional worsening (PϽ0.0001). Multivariate analysis identified diabetes as a predictor of poor vessel recanalization (Pϭ0.028). Low baseline National Institutes of Health Stroke Scale score was identified as a predictor of good or moderate clinical outcome (PϽ0.0001) and survival (Pϭ0.001) at 3 months, and younger age was identified as an additional predictor of survival (Pϭ0.012). For prediction of long-term clinical outcome, age was also an independent predictor (Pϭ0.018). Conclusions-In our series, intra-arterial thrombolysis as treatment of basilar artery occlusion was safe. National Institutes of Health Stroke Scale score at admission and age were identified as predictors of outcome, and these predictors should be considered for treatment allocation in future randomized trials.

Key Points• DDAVP is the drug of choice for mild hemophilia A and von Willebrand disease and (by unclear mechanisms) for platelet function disorders.• In vivo DDAVP selectively and markedly enhances the ability to form procoagulant platelets by enhancing intracellular Na 1 and Ca 21 fluxes.is clinically efficacious in patients with mild platelet function disorders but it is not known which mechanisms mediate this effect. Our aim was to evaluate the impact of in vivo DDAVP administration in these patients. We assessed von Willebrand factor (VWF), factor VIII, platelet activation and aggregation, platelet-dependent thrombin generation, and platelet intracellular Na 1 /Ca 21 fluxes, before and 2 and 4 hours after DDAVP (0.3 mg/kg). We found (1) no significant changes for P-selectin expression, PAC-1 binding, d-granule content and secretion, and platelet-aggregation; (2) significant decreases of secretion of a-granules and GPIIb-IIIa activation induced by adenosine 59-diphosphate, convulxin, and thrombin; (3) significant increases of procoagulant platelets induced by convulxin/thrombin and platelet-dependent thrombin generation; and (4) significant increases of intracellular Na 1 /Ca 21 concentrations. We show that in vivo DDAVP selectively and markedly enhances the ability to form procoagulant platelets and increases platelet-dependent thrombin generation by enhancing Na