Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand.
Eur J Haematol. 2017 Dec;99(6):520-524. doi: 10.1111/ejh.12965. Epub 2017 Oct 5.
Glanzmann thrombasthenia (GT) is an autosomal recessive platelet disorder, caused by defects of the platelet integrin αIIbβ3 (GPIIb/IIIa) resulting from pathogenic mutations in either ITGA2B or ITGB3. It is characterized by spontaneous mucocutaneous bleeding. The molecular features of GT in Thailand have not been identified. This study aimed to determine the clinical and molecular features of unrelated Thai patients with GT.
Four patients with clinically suspected GT were recruited at the Division of Pediatric Hematology/Oncology, King Chulalongkorn Memorial Hospital. The diagnosis was based on clinical and hematological parameters as well as genetic analysis. Whole exome sequencing (WES) was performed in all cases.
Of the four patients studied, the median age at first suspicion of GT was 2.5 years. All presented with severe bleeding symptoms (WHO bleeding scale 3). Flow cytometry to assess the surface GPIIb/IIIa complex showed reduced expression. By WES, we successfully identified seven mutant alleles in ITGA2B. One alteration, the c.2915dup (p.Leu973Alafs63), was detected in two unrelated families. One patient was homozygous for the c.617T>A (p.Val206Asp). Of the five different mutations, three have never been previously described. These include a missense, c.617T>A (p.Val206Asp), a deletion, c.1524_1533del (p.Gln508Hisfs3), and a nonsense, c.2344C>T (p.Arg782Ter).
This study reported three novel mutations expanding the genotypic spectrum of ITGA2B causing GT.
Glanzmann 血小板无力症（GT）是一种常染色体隐性血小板疾病，由血小板整合素 αIIbβ3（GPIIb/IIIa）缺陷引起，其致病突变位于 ITGA2B 或 ITGB3 基因中。其特征为自发性黏膜皮肤出血。泰国 GT 的分子特征尚未确定。本研究旨在确定泰国无关 GT 患者的临床和分子特征。
在朱拉隆功国王纪念医院儿科血液科/肿瘤科招募了 4 名临床疑似 GT 的患者。诊断基于临床和血液学参数以及基因分析。所有患者均进行了全外显子组测序（WES）。
在所研究的 4 名患者中，首次怀疑 GT 的中位年龄为 2.5 岁。所有患者均表现出严重的出血症状（WHO 出血量表 3 级）。评估表面 GPIIb/IIIa 复合物的流式细胞术显示表达减少。通过 WES，我们成功地在 ITGA2B 中发现了 7 个突变等位基因。两个不相关的家族中发现了一个改变，c.2915dup（p.Leu973Alafs63）。一位患者为 c.617T>A（p.Val206Asp）纯合子。在这五个不同的突变中，有三个是以前从未描述过的。包括错义突变 c.617T>A（p.Val206Asp）、缺失突变 c.1524_1533del（p.Gln508Hisfs3）和无义突变 c.2344C>T（p.Arg782Ter）。
本研究报道了三个新的突变，扩展了导致 GT 的 ITGA2B 的基因型谱。
