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A NOVEL CANDIDATE A/T789P MUTATION IDENTIFIED IN FIVE PATIENTS WITH TYPE 2N VON WILLEBRAND DISEASE FROM TWO DIFFERENT FAMILIES
Abstract number: P-W-169
Rastegar Lari1 G., Jazebi1 M., Guilliatt2 A.M., Short2 P.E., Enayat2 M.S., Ala1 F.A., Chapman3 O., Hill2 F.G.H.
11Molecular Genetics Laboratory, Iranian Hemophilia Treatment Center, Tehran, Iran (Islamic Republic of) 22Department of Haematology, The Children's Hospital, Birmingham 33Department of Haematology, Coventry & Warwick University Hospital, Coventry, United Kingdom
How-to-cite Rastegar Lari G, Jazebi M, Guilliatt AM, Short PE, Enayat MS, Ala FA, Chapman O, Hill FGH. A NOVEL CANDIDATE A/T789P MUTATION IDENTIFIED IN FIVE PATIENTS WITH TYPE 2N VON WILLEBRAND DISEASE FROM TWO DIFFERENT FAMILIES. J Thromb Haemost 2007; 5 Supplement 2: P-W-169
Abstract
Introduction: Type 2N von Willebrand disease (VWD) is characterised by a reduction in the affinity of von Willebrand factor (VWF) for factor VIII (FVIII) associated with mutations in the D' or D3 domain of the VWF gene. Presently only a few mutations are reported to cause a marked reduction in VIII:C binding (FVIII:CB) capacity.
Methods: Two siblings with a moderate reduction of FVIII:CB and their mother from a single UK family, and two relatives from a consanguinous Iranian family with severe reduction of FVIII:CB have been investigated. The Iranian patients had more severe bleeding symptoms than the UK patients. Exons 18 to 20 of the VWF gene were investigated by targeted direct DNA sequencing.
Results: In the Iranian patients FVIII:C was around 0.05U/ml and a homozygous 2365A>C transversion leading to T789P was identified in exon 18. In the UK family, the proband and her sister had a FVIII:C level of about 0.15U/ml and they were found to be heterozygous for the same 2365G>C (A789P) change in exon 18. This base change which is in the same codon as a common polymorphism (2365A>G; Thr/Ala) was not detected by direct DNA sequencing in 100 normal UK control alleles. In the two siblings of UK family, a second heterozygous transition of 2561G>A, leading to R854Q was detected in exon 20. When the mother of these patients was genetically analysed she was found to be heterozygous for 2365G>C (A789P), but not the second 2561G>A (R854Q) change. Therefore it is likely that the R854Q change is on a separate allele and inherited from the father who was not investigated.
Conclusions: In both families the presence of the A/T789P candidate mutation is linked with type 2N VWD. Further study of individuals from these two families will help to elucidate the individual effects of the two mutations on the FVIII binding capacity of VWF. Correct identification of the causative mutation and its tracking in the family can provide an accurate diagnosis and facilitate genetic counselling.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
Session Details
| Date: |
01/08/2007
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| Time: |
00:00-00:00
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| Session name: |
XXIst ISTH Congress |
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| Location: |
Oxford, UK |
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