Bernard-Soulier syndrome due to compound heterozygosity for a novel glycoprotein Ibβ mutation.
Bernard-Soulier syndrome due to compound heterozygosity for a novel glycoprotein Ibβ mutation.
复制标题
由于新型糖蛋白 Ibβ 突变的复合杂合性而导致 Bernard-Soulier 综合征。
DOI：
10.1159/000351057
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kusuhara K.
中科院分区：
文献类型：
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作者：
Sato T;Kunishima S;Shirayama R;Ichikawa S;Sakai M;Kusuhara K.
Bernard-Soulier 综合征 (BSS) 是一种常染色体隐性出血性疾病，其特征为血小板减少、巨大血小板和瑞斯托菌素诱导的血小板凝集缺失 [1, 2]。据估计，患病率低于百万分之一[3]。 BSS 患者的严重出血事件与创伤和外科手术有关；然而，出血的严重程度和频率因人而异[4]。 BSS 是由血小板糖蛋白 (GP) Ib/IX 复合物缺陷引起的。迄今为止，已描述了 GPIbα、GPIbβ 和 GPIX 基因中的 50 多种不同突变 [1, 2]。我们在此报告了一名 BSS 患者，其 GPIbβ 基因中存在新型复合杂合突变。女患者出生时胎龄35周零2天，出生体重1934克，因早产入住我院新生儿监护室。她是非近亲父母的第一个孩子。第一次抽血检查血小板计数为41×10 9/l，怀疑患有新生儿同种免疫性血小板减少症。因此，她接受了大剂量丙种球蛋白治疗，但血小板计数没有增加。住院期间，无脐出血、静脉穿刺部位出血等出血倾向。她的血小板计数保持在50-100×10 9/l。由于难以收集足够量的血液进行分析，因此没有对血小板减少症进行详细检查。此后，即使患者开始活动，也没有出现自发性出血。 3岁时，她被碎玻璃割伤手指，伤口缝了3针；然而，伤口的血却自行止住了。 4岁时，她因感冒后检查时偶然发现血小板减少症，经家庭医生转诊至我院。通过显微镜计数确定的血小板计数与她出生后一样低。首先通过仔细观察外周血涂片发现巨大血小板（血小板直径：3.9±1.1μm，对照受试者：2.5±0.3μm；n=31）。没有发现其他血液学异常。对巨血小板减少症进行了进一步检查。父亲和母亲的血小板计数分别为110-210×10 9/l和180-220×10 9/l。获得了父母的书面知情同意书，该研究得到了职业与环境健康大学和名古屋医疗中心伦理委员会的批准。
Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder characterized by thrombocytopenia, giant platelets, and absent ristocetin-induced platelet agglutination [1, 2]. The prevalence is estimated to be less than 1 in 1,000,000 [3]. Severe bleeding episodes in BSS patients are associated with trauma and surgical procedures; however, the severity and frequency of bleeding varies among individuals [4]. BSS is caused by defects in the platelet glycoprotein (GP) Ib/IX complex. More than 50 different mutations in the GPIbα, GPIbβ, and GPIX genes have been described so far [1, 2].We herein report a BSS patient with a novel compound heterozygous mutation in the GPIbβ gene. The female patient was born at a gestational age of 35 weeks and 2 days, and her birth weight was 1,934 g, so she was admitted to the neonatal care unit of our hospital due to prematurity. She was the first child of nonconsanguineous parents. At the first blood examination, the platelet count was 41× 10 9/l and she was suspected to have neonatal alloimmune thrombocytopenia. She therefore received high-dose gamma globulin therapy, but her platelet count did not increase. During the hospital stay, she had no bleeding tendencies such as omphalorrhagia or bleeding from the site of venipuncture. Her platelet count remained at 50-100× 10 9/l. A detailed examination of thrombocytopenia was not performed due to difficulty in collecting a sufficient amount of blood for analysis. Thereafter, the patient did not experience spontaneous bleeding, even after she became active. At 3 years of age, she cut her finger on broken glass and the wound required 3 stitches; however, the bleeding from the wound stopped spontaneously. At 4 years of age, she was referred to our hospital by a family doctor due to thrombocytopenia, which was discovered by chance when she was examined after having caught a cold. The platelet count as determined by microscopic counting was as low as it had been just after her birth. Giant platelets were first pointed out by careful observation of peripheral blood smears (platelet diameter: 3.9±1.1 µm, control subjects: 2.5±0.3 µm; n= 31). No other hematological abnormalities were noted. Further examination of the macrothrombocytopenia was conducted. The platelet counts of her father and mother were 110-210× 10 9/l and 180-220× 10 9/l, respectively. Written informed consent was obtained from the parents, and the study was approved by the ethics committees of the University of Occupational and Environmental Health and Nagoya Medical Center.