Blood Journal
Leading the way in experimental and clinical research in hematology

Brief Report
Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene

  1. Andrew D. Paterson1,2,*,
  2. Johanna M. Rommens1,3,
  3. Bhupinder Bharaj1,
  4. Jessica Blavignac4,
  5. Isidro Wong1,
  6. Maria Diamandis4,
  7. John S. Waye4,
  8. Georges E. Rivard5, and
  9. Catherine P. M. Hayward4,6,*
  1. 1Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON;
  2. 2Dalla Lana School of Public Health and Institute of Medical Sciences, University of Toronto, Toronto, ON;
  3. 3Molecular Genetics, University of Toronto, Toronto, ON;
  4. 4Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON;
  5. 5Hematology/Oncology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC; and
  6. 6Department of Medicine, McMaster University, Hamilton, ON

Abstract

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder linked to a region on chromosome 10 that includes PLAU, the urokinase plasminogen activator gene. QPD increases urokinase plasminogen activator mRNA levels, particularly during megakaryocyte differentiation, without altering expression of flanking genes. Because PLAU sequence changes were excluded as the cause of this bleeding disorder, we investigated whether the QPD mutation involved PLAU copy number variation. All 38 subjects with QPD had a direct tandem duplication of a 78-kb genomic segment that includes PLAU. This mutation was specific to QPD as it was not present in any unaffected family members (n = 114), unrelated French Canadians (n = 221), or other persons tested (n = 90). This new information on the genetic mutation will facilitate diagnostic testing for QPD and studies of its pathogenesis and prevalence. QPD is the first bleeding disorder to be associated with a gene duplication event and a PLAU mutation.

  • Submitted July 26, 2009.
  • Accepted November 12, 2009.
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