一名成年迟发性血栓性血小板减少性紫癜患者的新型ADAMTS - 13突变
Novel ADAMTS-13 mutations in an adult with delayed onset thrombotic thrombocytopenic purpura.
作者信息
Tao Z, Anthony K, Peng Y, Choi H, Nolasco L, Rice L, Moake J L, Dong J-F
机构信息
Section of Thrombosis Research, Baylor College of Medicine, Houston, TX 77030, USA.
出版信息
J Thromb Haemost. 2006 Sep;4(9):1931-5. doi: 10.1111/j.1538-7836.2006.02098.x. Epub 2006 Jun 22.
BACKGROUND
Thrombotic thrombocytopenic purpura (TTP) is associated with congenital and acquired deficiency of ADAMTS-13, a metalloprotease that cleaves von Willebrand factor (VWF) and reduces its adhesive activity. Mutations throughout the ADAMTS13 gene have been identified in congenital TTP patients, most of whom have initial episodes during infancy or in early childhood.
PATIENTS AND METHODS
We report the case of an adult male who was diagnosed with idiopathic thrombocytopenic purpura at age 34, and with TTP 14 years later. The patient was compound heterozygous for an 18 bp in-frame deletion (C365del) in the disintegrin domain and a point mutation of R1060W in the seventh thrombospondin domain of the ADAMTS-13 gene.
CONCLUSIONS
In vitro studies found that C365del and R1060W severely impair ADAMTS-13 synthesis in transfected Hela cells, whereas the deletion mutant also failed to cleave VWF under static and flow conditions.
背景
血栓性血小板减少性紫癜（TTP）与先天性和获得性ADAMTS - 13缺乏有关，ADAMTS - 13是一种金属蛋白酶，可裂解血管性血友病因子（VWF）并降低其黏附活性。先天性TTP患者中已鉴定出ADAMTS13基因的多处突变，其中大多数患者在婴儿期或儿童早期首次发病。
患者与方法
我们报告一例成年男性病例，该患者34岁时被诊断为特发性血小板减少性紫癜，14年后诊断为TTP。该患者为ADAMTS - 13基因解整合素结构域18bp框内缺失（C365del）和第七个血小板反应蛋白结构域R1060W点突变的复合杂合子。
结论
体外研究发现，C365del和R1060W严重损害转染的Hela细胞中ADAMTS - 13的合成，而缺失突变体在静态和流动条件下也无法裂解VWF。
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