Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada.
Blood. 2010 Feb 11;115(6):1264-6. doi: 10.1182/blood-2009-07-233965. Epub 2009 Dec 9.
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.
魁北克血小板功能紊乱症（QPD）是一种常染色体显性出血性疾病，与包括尿激酶纤溶酶原激活物基因（PLAU）在内的 10 号染色体区域相关。QPD 增加了尿激酶纤溶酶原激活物 mRNA 水平，尤其是在巨核细胞分化过程中，但不改变侧翼基因的表达。由于排除了 PLAU 序列改变是导致这种出血性疾病的原因，我们研究了 QPD 突变是否涉及 PLAU 拷贝数变异。所有 38 名 QPD 患者均存在 PLAU 在内的 78kb 基因组片段的直接串联重复。该突变是 QPD 所特有的，因为它不存在于任何未受影响的家族成员（n=114）、无关的法国裔加拿大人（n=221）或其他受检者（n=90）中。关于这种基因突变的新信息将有助于 QPD 的诊断检测，以及其发病机制和流行率的研究。QPD 是首个与基因重复事件和 PLAU 突变相关的出血性疾病。
