An Alu-mediated novel large deletion is the most frequent cause of type 3 von Willebrand disease in Hungary.

BACKGROUND: We studied 24 Hungarian patients from 23 unrelated families to identify the genetic background of the entire type 3 von Willebrand disease (VWD) population in this country. The current report focuses on the molecular characterization of a novel large deletion. RESULTS: A large partial deletion (delExon1-3) of the 5'-region of the von Willebrand factor gene (VWF) was detected in 12/48 alleles (25% of all type 3 alleles). The 5'-deletion breakpoint is located in the untranslated region between VWF and CD9, whereas the 3' breakpoint is in intron 3 of VWF. Analysis of the breakpoints showed Alu Y and Alu SP repetitive sequences at the ends of the deletion, suggesting that a recombination event caused the subsequent loss of the 35-kb fragment. DelExon1-3 was not found in any of the other screened populations. CONCLUSION: We report a large novel deletion including exons 1, 2 and 3 of VWF commonly causing type 3 VWD in the Hungarian population. This mutation, probably caused by an Alu-mediated recombination event, and subsequently distributed in Hungary by a founder effect, seems to be unique to Hungarian patients with a high allele frequency. Together, delExon1-3 and 2435delC make up 37.5% of the genetic defects in Hungarian patients with VWD type 3. This offers a rational approach to molecular testing of relevant families in Hungary.

Association between early onset and organ manifestations of systemic lupus erythematosus (SLE) and a down-regulating promoter polymorphism in the MBL2 gene.

The serum concentration of mannose-binding lectin (MBL) is genetically determined by a series of allelic polymorphisms in the MBL2 gene. Since several polymorphisms of the MBL2 gene have been suggested to be risk locus for systemic lupus erythematosus (SLE), we investigated MBL2 polymorphisms in 315 SLE patients from Hungary and 182 geographically matched healthy controls. Within the group of patients, we found that homozygotes for an MBL2 down-regulating promoter polymorphism at position -221 (YA to XA) (rs7096206) were significantly (p=0.017) younger at diagnosis than the other patients. The frequency of juvenile-onset SLE (

Thrombosis risk in systemic lupus erythematosus: the role of thrombophilic risk factors.

OBJECTIVES: Thromboembolic episodes are frequent manifestations of systemic lupus erythematosus (SLE). Although the presence of anti-phospholipid antibodies (aPL) is known to contribute to thromboembolism (TE), the relative contribution of other TE risk factors is unknown. The aim of this study was to determine the prevalence of TE in a Caucasian SLE population, to identify the risk factors of highest importance, and to assess the clinical value of thrombophilia screening among SLE patients. METHODS: Samples from 105 patients were analysed with a screen including aPL, activated protein C resistance, factor V Leiden (FVL) and prothrombin G20210A mutations; protein C, protein S and antithrombin activity; factor VIII (FVIII) and von Willebrand factor (vWF), and homocysteine (Hcy) levels. RESULTS: The annual incidence of arterial and venous TE events in our SLE population was 5.4 and 12.4 per 1000, respectively. The highest risk of thrombosis was carried by the simultaneous presence of lupus anticoagulant (LA) and anti-cardiolipin (aCL) [relative risk (RR) = 4.03, 95% confidence interval (CI) 2.06-7.86] or anti-beta2-glycoprotein I antibodies (abeta2-GPI) (RR = 5.10, 95% CI 2.58-10.1). Positivity for the individual aPL tests all carried an elevated TE risk. The presence of other risk factors seemed to be of less importance. CONCLUSIONS: In SLE patients, the presence of aPL is a more significant risk factor for the development of thrombosis than the known inherited deficiencies. Based on these data, routine screening for additional hereditary risk factors seems to be unwarranted.