| |
|
|
|
|
|
|
|||
|
Blood, 12 February 2009, Vol. 113, No. 7, pp. 1543-1546. Prepublished online as a Blood First Edition Paper on November 6, 2008; DOI 10.1182/blood-2008-08-175216.
Submitted August 26, 2008
Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada * Corresponding author; email: haywrdc{at}mcmaster.ca.
Quebec platelet disorder (QPD) is an autosomal dominant disorder, with high penetrance, that is associated with increased risks for bleeding. The hallmark of QPD is a gain-of-function defect in fibrinolysis due to increased platelet content of urokinase plasminogen activator (uPA), without systemic fibrinolysis. We hypothesized that increased expression of uPA by differentiating QPD megakaryocytes is linked to PLAU. Genetic marker analyses indicated that QPD was significantly linked to a 2 Megabase region on chromosome 10q containing PLAU with a maximum multi-point LOD score= 11 between markers D10S1432 and D10S1136. Analysis of PLAU, by sequencing and Southern blotting, excluded mutations within PLAU and its known regulatory elements as the cause of QPD. Analyses of uPA mRNA indicated that QPD distinctly increased transcript levels of the linked PLAU allele with megakaryocyte differentiation. These findings implicate a mutation in an uncharacterized cis element near PLAU as the cause of QPD.
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Copyright © 2008 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||