Source:http://linkedlifedata.com/resource/pubmed/id/19372260
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2009-7-31
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| pubmed:abstractText |
Direct sequencing of VWF genomic DNA in 21 patients with type 3 von Willebrand disease (VWD) failed to reveal a causative homozygous or compound heterozygous VWF genotype in 5 cases. Subsequent analysis of VWF mRNA led to the discovery of a deletion (c.221-977_532 + 7059del [p.Asp75_Gly178del]) of VWF in 7 of 12 white type 3 VWD patients from 6 unrelated families. This deletion of VWF exons 4 and 5 was absent in 9 patients of Asian origin. We developed a genomic DNA-based assay for the deletion, which also revealed its presence in 2 of 34 type 1 VWD families, segregating with VWD in an autosomal dominant fashion. The deletion was associated with a specific VWF haplotype, indicating a possible founder origin. Expression studies indicated markedly decreased secretion and defective multimerization of the mutant VWF protein. Further studies have found the mutation in additional type 1 VWD patients and in a family expressing both type 3 and type 1 VWD. The c.221-977_532 + 7059del mutation represents a previously unreported cause of both types 1 and 3 VWD. Screening for this mutation in other type 1 and type 3 VWD patient populations is required to elucidate further its overall contribution to VWD arising from quantitative deficiencies of VWF.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
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| pubmed:issn |
1528-0020
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
30
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| pubmed:volume |
114
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1091-8
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:19372260-Adolescent,
pubmed-meshheading:19372260-Adult,
pubmed-meshheading:19372260-Aged,
pubmed-meshheading:19372260-Aged, 80 and over,
pubmed-meshheading:19372260-Asian Continental Ancestry Group,
pubmed-meshheading:19372260-England,
pubmed-meshheading:19372260-European Continental Ancestry Group,
pubmed-meshheading:19372260-Exons,
pubmed-meshheading:19372260-Female,
pubmed-meshheading:19372260-Founder Effect,
pubmed-meshheading:19372260-Genes, Dominant,
pubmed-meshheading:19372260-Genotype,
pubmed-meshheading:19372260-Haplotypes,
pubmed-meshheading:19372260-Humans,
pubmed-meshheading:19372260-Male,
pubmed-meshheading:19372260-Middle Aged,
pubmed-meshheading:19372260-Recombinant Fusion Proteins,
pubmed-meshheading:19372260-Sequence Analysis, DNA,
pubmed-meshheading:19372260-Sequence Deletion,
pubmed-meshheading:19372260-Young Adult,
pubmed-meshheading:19372260-von Willebrand Diseases,
pubmed-meshheading:19372260-von Willebrand Factor
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| pubmed:year |
2009
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| pubmed:articleTitle |
A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3.
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| pubmed:affiliation |
University Department of Haematology, Manchester Royal Infirmary, Manchester, M13 9WL, United Kingdom.
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| pubmed:publicationType |
Journal Article
|