Document Details

Document Type : Article In Journal 
Document Title :
Anovel vonWillebrand disease–causing mutation (Arg273Trp) Anovel vonWillebrand disease–causing mutation (Arg273Trp) multimerization and secretion
Anovel vonWillebrand disease–causing mutation (Arg273Trp) Anovel vonWillebrand disease–causing mutation (Arg273Trp) multimerization and secretion
 
Document Language : English 
Abstract : In this report we describe the molecular defect underlying partial and severe quantitative von Willebrand factor (VWF) deficiencies in 3 families previously diagnosed with types 1 and 3 Von Willebranddisease. Analysis of the VWF gene in affected family members revealed a novel C to T transition at nucleotide 1067 of the VWF complemetary DNA (cDNA), predicting substitution of arginine by tryptophan at amino acid position 273 (R273W) of pre–pro-VWF. Two patients, homozygous for the R273W mutation, had a partial VWF deficiency (VWF:Ag levels of 0.06 IU/mL and 0.09 IU/mL) and lacked highmolecular weight VWF multimers in plasma. A third patient, also homozygous for the R273W mutation, had a severe VWF deficiency (VWF:Ag level of less than 0.01 IU/mL) and undetectable VWF multimers in plasma. Recombinant VWF having the R273W mutation was expressed in COS-7 cells. Pulse-chase experiments showed that secretion of rVWFR273W was severely impaired compared with wild-type rVWF. However, the mutation did not affect the ability of VWF to form dimers in the endoplasmic reticulum (ER). Multimer analysis showed that rVWFR273W failed to form high-molecular- weight multimers present in wild-type rVWF. We concluded that the R273W mutation is responsible for the quantitative VWF deficiencies and aberrant multimer patterns observed in the affected family members. To identify factors that may function in the intracellular retention of rVWFR273W, we investigated the interactions of VWF expressed in COS-7 cells with molecular chaperones of the ER. The R273W mutation did not affect the ability of VWF to bind to BiP, Grp94, ERp72, calnexin, and calreticulin in COS-7 cells. 
ISSN : 1528-0020 
Journal Name : Blood. 
Volume : 96 
Issue Number : 2 
Publishing Year : 1421 AH
2000 AD 
Article Type : Article 
Added Date : Sunday, April 25, 2010 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Simon AllenAllen, Simon InvestigatorDoctoratesimon.allen@sheffield.ac.uk
عادل أبو زنادةAbuzenadah, Adel ResearcherDoctorate 

Back To Researches Page