Kunishima S, Tomiyama Y, Honda S, Kurata Y, Kamiya T, Ozawa K, Saito H
Japanese Red Cross Aichi Blood Centre, Seto, Aichi, Japan.
Br J Haematol. 1999 Dec;107(3):539-45. doi: 10.1046/j.1365-2141.1999.01733.x.
Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder due to quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex, the platelet receptor for von Willebrand factor. We describe here the genetic basis of the disorder in a patient with BSS. Flow cytometric analysis of the patient's platelets showed a greatly reduced GPIbalpha and completely absent GPIX surface expression. Immunoblot analysis disclosed greatly reduced GPIbalpha and residual amounts of GPIbbeta and GPIX in the platelets. DNA sequencing analysis revealed the patient to be homozygous for a novel missense mutation in the GPIX gene that converts Cys (TGT) to Tyr (TAT) at residue 97. Transient transfection studies confirmed that mutant GPIX was not expressed on the transfected cells, showing that the mutation was responsible for the BSS phenotype observed in the patient.
伯纳德-索利尔综合征（BSS）是一种常染色体隐性出血性疾病，由糖蛋白（GP）Ib/IX/V复合物（血管性血友病因子的血小板受体）的数量或质量异常引起。我们在此描述一名BSS患者该疾病的遗传基础。对患者血小板进行流式细胞术分析显示，糖蛋白Ibα（GPIbalpha）显著减少，糖蛋白IX（GPIX）表面表达完全缺失。免疫印迹分析表明，血小板中GPIbalpha显著减少，GPIbbeta和GPIX残留少量。DNA测序分析显示，患者GPIX基因存在一个新的错义突变，该突变使第97位氨基酸的半胱氨酸（TGT）转变为酪氨酸（TAT），呈纯合状态。瞬时转染研究证实，突变型GPIX在转染细胞上未表达，表明该突变导致了患者所观察到的BSS表型。
