Koskela S, Partanen J, Salmi T T, Kekomäki R
Finnish Red Cross Blood Transfusion Service, Helsinki, Finland.
Eur J Haematol. 1999 Mar;62(3):160-8. doi: 10.1111/j.1600-0609.1999.tb01739.x.
Bernard-Soulier syndrome (BSS) is a rare hereditary bleeding disorder and macrothrombocytopenia which is caused by a defect in the platelet glycoprotein Ib/IX/V (GP Ib/IX/V) complex, the receptor for von Willebrand factor and thrombin. Here we report the molecular basis of the classical form of BSS in two unrelated Finnish patients, both with a life-long history of severe bleeding. Flow cytometry and immunoblotting showed no expression of GP Ib/IX, GP Ib alpha, GP Ib beta or GP IX (less than 10%) in the patients' platelets. No expression of GP V (< 10%) was observed in propositus 1, but a residual amount was found in propositus 2 (24%). DNA sequencing analysis revealed that propositus 1 was compound heterozygous for a two-base-pair deletion at Tyr505(TAT) and a point mutation Leu129(CTC)Pro(CCC) in the GP Ib alpha gene. Propositus 2 was homozygous for the Tyr505(TAT) deletion. The nine relatives who were heterozygous for either of the mutations also had low levels of GP Ib alpha (74-90%). Hence, Bernard-Soulier patients homozygous or compound heterozygous for Tyr505(TAT) are severely affected. Interestingly, both mutations have independently been found in three other families in previous reports, suggesting their ancient age or mutational 'hot spot'.
伯纳德-索利尔综合征（BSS）是一种罕见的遗传性出血性疾病和大血小板减少症，由血小板糖蛋白Ib/IX/V（GP Ib/IX/V）复合物缺陷引起，该复合物是血管性血友病因子和凝血酶的受体。在此，我们报告了两名无亲缘关系的芬兰患者中经典型BSS的分子基础，这两名患者均有终生严重出血史。流式细胞术和免疫印迹显示，患者血小板中未表达GP Ib/IX、GP Ibα、GP Ibβ或GP IX（低于10%）。在先证者1中未观察到GP V的表达（<10%），但在先证者2中发现了残留量（24%）。DNA测序分析显示，先证者1在GP Ibα基因的Tyr505（TAT）处有一个两碱基对缺失和一个点突变Leu129（CTC）Pro（CCC），为复合杂合子。先证者2为Tyr505（TAT）缺失的纯合子。这两种突变的九名杂合子亲属的GP Ibα水平也较低（74-90%）。因此，Tyr505（TAT）纯合或复合杂合的伯纳德-索利尔患者受到严重影响。有趣的是，在之前的报告中，这两种突变在其他三个家族中均独立发现，提示它们存在时间久远或为突变“热点”。
