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postgraduate thesis: Genotypic characterisation of type 2 von Willebrand disease

TitleGenotypic characterisation of type 2 von Willebrand disease
Authors
Issue Date2013
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Tsui, S. [崔詩珮]. (2013). Genotypic characterisation of type 2 von Willebrand disease. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5091500
Abstractvon Willebrand disease (VWD) is the most common autosomal bleeding disorder. It is divided into type 1, 2 and 3. Type 2 VWD shows qualitative defects in VWF and is further sub-classified into type 2A, 2B, 2M and 2N, each having different functional defects in VWF. Most of the associated mutations are located at the exons in VWF which encode for the affected functional domains. Diagnosis of VWD is currently based on history and phenotypic tests, which can be difficult often times. Therefore, molecular diagnosis of type 2 VWD is an attractive alternative. There are only a few genotypic characterisation studies of type 2 VWD in Chinese. This study aims to provide genetic data of type 2 VWD in Hong Kong. Archive DNA samples of 21non-type 2N type 2 VWD patients (Group 1), 15 type 2N/mild haemophilia A (HA) patients (Group2) and 35 control subjects were recruited. VWF exon 27, 28 and exon 18, 19, 20, 23, 24 were Sanger sequenced in Group 1 and Group 2 subjects, respectively. All seven exons were sequenced in the control subjects. Seven of 21 Group 1 subjects were found to have pathogenic mutation sin exon 28, with 2being novel. Only 1 Group 2 subject was found to be heterozygous for a novel non-synonymous variation at exon 23, the significance of which could not be ascertained. Sixteen benign polymorphisms were detected from exons sequenced in patients and controls. The low pathogenic mutation detection rate may suggest that the pattern of mutation in Chinese is different from other populations. The possibility of misdiagnosis in a proportion of these patients cannot be excluded in view of the known difficulty in patient ascertainment in VWD and the limited phenotypic diagnostic tools available in Hong Kong. Further studies of other exons are indicated to document the mutation spectrum of type 2 VWD in our Chinese population. RNA work and functional studies are required to fully characterise novel sequence variations found. High throughput mutation detection platforms and better phenotypic characterisation will facilitate the introduction of VWD genotyping into routine clinical diagnostics.
DegreeMaster of Medical Sciences
SubjectVon Willebrand disease - China - Hong Kong - Genetic aspects
Dept/ProgramPathology
Persistent Identifierhttp://hdl.handle.net/10722/193528

 

DC FieldValueLanguage
dc.contributor.authorTsui, Sze-pui-
dc.contributor.author崔詩珮-
dc.date.accessioned2014-01-13T23:10:33Z-
dc.date.available2014-01-13T23:10:33Z-
dc.date.issued2013-
dc.identifier.citationTsui, S. [崔詩珮]. (2013). Genotypic characterisation of type 2 von Willebrand disease. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5091500-
dc.identifier.urihttp://hdl.handle.net/10722/193528-
dc.description.abstractvon Willebrand disease (VWD) is the most common autosomal bleeding disorder. It is divided into type 1, 2 and 3. Type 2 VWD shows qualitative defects in VWF and is further sub-classified into type 2A, 2B, 2M and 2N, each having different functional defects in VWF. Most of the associated mutations are located at the exons in VWF which encode for the affected functional domains. Diagnosis of VWD is currently based on history and phenotypic tests, which can be difficult often times. Therefore, molecular diagnosis of type 2 VWD is an attractive alternative. There are only a few genotypic characterisation studies of type 2 VWD in Chinese. This study aims to provide genetic data of type 2 VWD in Hong Kong. Archive DNA samples of 21non-type 2N type 2 VWD patients (Group 1), 15 type 2N/mild haemophilia A (HA) patients (Group2) and 35 control subjects were recruited. VWF exon 27, 28 and exon 18, 19, 20, 23, 24 were Sanger sequenced in Group 1 and Group 2 subjects, respectively. All seven exons were sequenced in the control subjects. Seven of 21 Group 1 subjects were found to have pathogenic mutation sin exon 28, with 2being novel. Only 1 Group 2 subject was found to be heterozygous for a novel non-synonymous variation at exon 23, the significance of which could not be ascertained. Sixteen benign polymorphisms were detected from exons sequenced in patients and controls. The low pathogenic mutation detection rate may suggest that the pattern of mutation in Chinese is different from other populations. The possibility of misdiagnosis in a proportion of these patients cannot be excluded in view of the known difficulty in patient ascertainment in VWD and the limited phenotypic diagnostic tools available in Hong Kong. Further studies of other exons are indicated to document the mutation spectrum of type 2 VWD in our Chinese population. RNA work and functional studies are required to fully characterise novel sequence variations found. High throughput mutation detection platforms and better phenotypic characterisation will facilitate the introduction of VWD genotyping into routine clinical diagnostics.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshVon Willebrand disease - China - Hong Kong - Genetic aspects-
dc.titleGenotypic characterisation of type 2 von Willebrand disease-
dc.typePG_Thesis-
dc.identifier.hkulb5091500-
dc.description.thesisnameMaster of Medical Sciences-
dc.description.thesislevelMaster-
dc.description.thesisdisciplinePathology-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5091500-
dc.date.hkucongregation2013-

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