Von Willebrand disease (VWD) is a common bleeding disorder caused by either
quantitative (type1 and 3) or qualitative (type 2) defects of von Willebrand factor
(VWF). The diagnosis of VWD usually requires a panel of tests. Several
analyses therefore are required to diagnose VWD. These tests are also
subjected to pitfalls and it is important to take the pitfalls in to consideration
when diagnosing VWD. Despite all these tests, the diagnosis and classification
of VWD often remains a challenge. Identification of mutations that cause
functional defects of VWF (type 2 VWD) is needed to improve the diagnosis of
the disease. Mutations that cause functional abnormalities of VWF occur mostly
in exon 28 of the VWF gene. Exon 28 primarily encodes the platelet GPIb and
collagen binding domains of VWF (A1 domains) and the ADAMTS13 cleavage
domain (A2 domains). Recently, studies in industrialised countries have been
conducted on finding mutations on exon 28 but none have been done on South
African populations. In this study we searched for mutations in exon 28 of the
VWF gene in 5 patients with functional defects of VWF in order to set up the
method for genetic analysis of VWD. We used two patients with type 2M, two
with type 2B and one with type 2A VWD in this study. The whole exon 28 was
analysed in four specific fragments, using PCR with primers that mismatch the
pseudogene. The mutations were identified by automatic sequencing of the
different fragments. The following polymorphisms were detected. A silent SNP
4641T/C in all five patients, the SNP 4141A/G in three patients, a silent SNP
3795G/A in one patient and a novel silent SNP 4923G/A in another patient. It is
important to note that we found a novel SNP in an African patient with type 2B
VWD, since no polymorphisms reported in exon 28 were from African
populations. Several studies have proven the importance of mutational analysis
is solving laboratory diagnosis paradox. The mutations found in the patients
with type 2 VWD confirm the diagnosis and validates the importance of
molecular diagnosis in VWD. With this study, we have successfully
implemented a method to detect mutations in exon 28 of the VWF gene.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ufs/oai:etd.uovs.ac.za:etd-01282010-111937 |
| Date | 28 January 2010 |
| Creators | Mothabeng, Maliengoane Sylvia |
| Contributors | Dr A de Kock, Prof SM Meiring |
| Publisher | University of the Free State |
| Source Sets | South African National ETD Portal |
| Language | en-uk |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.uovs.ac.za//theses/available/etd-01282010-111937/restricted/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University Free State or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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