Anne C Goodeve

..This review explores the genetic basis of each VWD type, relating mutations identified to disease mechanism. Additionally, utility of genetic analysis within the different disease types is explored...

..This article thus highlights both the molecular basis of hemophilia and some of the additional information that can be gained from determination of the mutation responsible for hemophilia in affected patients...

..These results may enable patients at higher risk of inhibitor formation to be identified. This may have consequences for the design of clinical trials and treatment options available to high-risk patients...

..To avoid confusion with previously used numbering schemes for mature VWF, which started from serine 764 of pre-pro VWF, the use of the single letter amino acid code is recommended...

..About one third of the type 1 VWD cases recruited could be reconsidered as type 2. The remaining group could be considered "true" type 1 VWD, although mutations were found in only 55%...

..Type 1 von Willebrand disease (VWD) is the most common form of VWD, but has remained [corrected] the least well understood. Recent work is changing this situation. This review summarizes recent analysis of the genetic basis of the disease...

..Guidelines on undertaking and reporting the testing plus external quality assessment are now available to help ensure that genetic analysis yields accurate and well-interpreted results...

..Understanding potential confounding factors including heparin and residual FVIII in test plasma, plus optimal standardization can reduce assay coefficient of variation to 10-20%.These areas are all explored within this article...

..Our results provide further evidence for locus heterogeneity in type 1 VWD...

..6%) with t(8;21) AML. All mutations were mutually exclusive; 40% of inv(16) AML patients possessed either a c-KIT or FLT3 mutation. c-KIT exon 8 mutations were shown to be a significant factor adversely affecting relapse rate...

....

..Therefore, in contrast to acute myeloid leukaemia, mutations in RTKs class III do not appear to play a significant pathogenetic role in idiopathic myelofibrosis...

..This may lead to enhanced cell survival, and therefore contribute to pathogenesis of the disease. Trb-1/trb-2 may, therefore, represent useful therapeutic targets for the treatment of AML in patients with dys-regulated trb activity...

..Conformation sensitive gel electrophoresis was found to be technically simple and efficient at locating previously unknown FVIII gene mutations...

..For families remaining uninformative by these procedures, a range of point mutation screening techniques is available. Dedicated electrophoresis equipment is enabling use of these techniques to become more widespread...

..These two individuals therefore have compound heterozygous VWD in which the only expressed allele has a type 2N mutation. In our population, such compound heterozygosity appears to be a significant cause of type 2N VWD...

..Blood. 2000;95:2000-2007)..

..These alterations to the analysis enhance the universal applicability of these polymorphisms, as was demonstrated by a comparative study in Caucasian and Thai females...

..The R273W mutation did not affect the ability of VWF to bind to BiP, Grp94, ERp72, calnexin, and calreticulin in COS-7 cells. (Blood. 2000;96:560-568)..

..In contrast there was no apparent difference between rVWFR273W and wild-type rVWF in their time-courses of interaction with calreticulin...

..Studies of pseudo-WPB formation in this system thus yield insights into the structure-function relationships underpinning the ability of VWF to form functional WPBs...

....