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

• Published in: Blood Vol. 115; no. 6; pp. 1264 - 1266
• Main Authors: Paterson, Andrew D., Rommens, Johanna M., Bharaj, Bhupinder, Blavignac, Jessica, Wong, Isidro, Diamandis, Maria, Waye, John S., Rivard, Georges E., Hayward, Catherine P.M.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 11.02.2010; Americain Society of Hematology
• Subjects: Adult; Base Sequence; Biological and medical sciences; Blood Platelet Disorders - blood; Blood Platelet Disorders - diagnosis; Blood Platelet Disorders - genetics; Chromosomes, Human, Pair 10 - genetics; Female; Gene Dosage; Gene Duplication; Hematologic and hematopoietic diseases; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Male; Medical sciences; Molecular Sequence Data; Prognosis; Sequence Homology, Nucleic Acid; Urokinase-Type Plasminogen Activator - genetics; Peptidases; u-Plasminogen activator; Serine endopeptidases; Gene; Hematology; Enzyme; Hydrolases; Genetics; Factor V Quebec; Tandemly repeated sequence; Thrombocytopathy
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2009-07-233965

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.