Center of Excellence In Genomic Medicine Research | Researches | Two novel type 2N vonWillebrand disease–causing mutations that result in defective factor VIII binding, multimerization, and secretion of vonWillebrand factor.

Center of Excellence In Genomic Medicine Research

Document Details

Document Type	:	Article In Journal
Document Title	:	Two novel type 2N vonWillebrand disease–causing mutations that result in defective factor VIII binding, multimerization, and secretion of vonWillebrand factor. Two novel type 2N vonWillebrand disease–causing mutations that result in defective factor VIII binding, multimerization, and secretion of vonWillebrand factor
Document Language	:	English
Abstract	:	Two novel mutations, a T-to-C transition at nucleotide 2612 and a T-to-G transversion at nucleotide 3923 of the von Willebrand factor (vWF) complementary DNA, were detected by analysis of the vWF gene in DNA from members of 2 families with atypical vonWillebrand disease. The T2612C transition predicts substitution of cysteine by arginine at amino acid position 788 (C788R), and the T3923G transversion predicts substitution of cysteine by glycine at position 1225 (C1225G) of pre-pro-vWF. The patients homozygous for the C788R and C1225G mutations both had a partial vWF deficiency (0.18 IU/mL and 0.07 IU/mL vWF antigen, respectively); vWF in plasma from patients homozygous for either the C788R or the C1225G mutation failed to bind factor VIII and lacked high molecular weight multimers. Recombinant (r) vWF molecules having the C788R or C1225G mutation were expressed in COS-7 cells. Both rvWF C788R and rvWF C1225G exhibited significantly impaired secretion and failed to bind factor VIII. Recombinant vWF C788R in COS-7 culture medium showed a severe reduction in high molecular weight multimers, whereas rvWF C1225G showed a very mild reduction in high molecular weight multimers when compared with wild-type rvWF.
ISSN	:	1528-0020
Journal Name	:	Blood.
Volume	:	95
Issue Number	:	6
Publishing Year	:	1420 AH 1999 AD
Article Type	:	Article
Added Date	:	Sunday, April 25, 2010

Researchers

Researcher Name (Arabic)	Researcher Name (English)	Researcher Type	Dr Grade	Email
Simon Allen	Allen, Simon	Investigator	Doctorate	simon.allen@sheffield.ac.uk
عادل أبو زنادة	Abuzenadah, Adel	Researcher	Doctorate

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