Linked Life Data

1537829

Source:http://linkedlifedata.com/resource/pubmed/id/1537829

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1992-4-2
pubmed:abstractText
Type IIA von Willebrand disease (vWD) results from abnormalities in von Willebrand factor (vWF) characterized by absence of plasma high molecular weight (HMW) vWF multimers. In this report, 5 distinct point mutations were identified in 6 Type IIA vWD families. A total of 7 mutations, all clustered within a 124-amino acid segment of the vWF A2 domain, now account for 9 of a panel of 11 Type IIA families. In COS-7 cells, 3 single amino acid substitutions, Val844----Asp, Ser743----Leu, and Gly742----Arg, impaired the transport of vWF multimers between the endoplasmic reticulum and the Golgi complex, with more profound effects on the secretion of HMW multimers than lower molecular weight forms. In contrast, 2 substitutions, Arg834----Trp and Gly742----Glu, resulted in secretion of HMW multimers similar to wild-type vWF. The vWF structure observed within patient platelets correlated closely with the synthesis pattern seen for the corresponding mutants in COS-7 cells. These findings demonstrate that structural alterations within the A2 domain of vWF can produce the characteristic phenotype of Type IIA vWD via two distinct molecular mechanisms.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4424-30
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Impaired intracellular transport produced by a subset of type IIA von Willebrand disease mutations.
pubmed:affiliation
Howard Hughes Medical Institute, Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109-0650.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't