National Institute of Blood Disease and Bone Marrow Transplantation, Karachi 75300, Pakistan.
Baqai Institute of Hematology, Baqai Medical University, Karachi 75340, Pakistan.
Cells. 2023 Jan 4;12(2):213. doi: 10.3390/cells12020213.
Glanzmann thrombasthenia (GT) is a rare autosomal recessive inherited platelet disorder occurring frequently in populations with high incidence of consanguineous marriages. GT is characterized by quantitative and/or qualitative defect of the platelet αIIbβ3 (GPIIb/IIIa) receptor caused by pathogenic variants of the encoding genes: and . Patients present with a moderate to severe bleeding tendency with normal platelet count. Platelets show reduced/absent aggregation for all agonists except ristocetin in light transmission aggregometry and reduced/absent αIIbβ3 expression in flow cytometry (FC). In this study, we investigated a cohort of 20 Pakistani patients and 2 families collected from the National Institute of Blood Disease, Karachi and Chughtai's Lab, Lahore. Platelet aggregation studies, FC (platelet CD41, CD61, CD42a, CD42b) and direct sequencing of the candidate genes were performed. All patients showed altered platelet aggregation, but normal agglutination after stimulation with ristocetin. Absent/reduced αIIbβ3 receptor expression was present in the platelets of 16 patients, in 4 patients expression was borderline/normal. Candidate gene sequencing identified pathogenic/likely pathogenic variants in 15 patients. Seven variants are novel. One patient with absent receptor expression remained without genetic finding. 13 (86.7%) of 15 patients stated consanguinity reflected by homozygosity finding in 14 (93.3%) patients.
血管性血友病因子血小板无力症（GT）是一种罕见的常染色体隐性遗传性血小板疾病，在高发近亲结婚人群中频繁发生。GT 的特征是由编码基因的致病变异引起的血小板 αIIbβ3（GPIIb/IIIa）受体的数量和/或质量缺陷：和 。患者表现为血小板计数正常但存在中重度出血倾向。在透光比浊聚集试验中，除瑞斯托霉素外，所有激动剂诱导的血小板聚集减少/缺失，在流式细胞术（FC）中 αIIbβ3 表达减少/缺失。在这项研究中，我们调查了来自卡拉奇国家血液疾病研究所和拉合尔 Chughtai 实验室的 20 名巴基斯坦患者和 2 个家系。进行了血小板聚集研究、FC（血小板 CD41、CD61、CD42a、CD42b）和候选基因的直接测序。所有患者均表现出改变的血小板聚集，但瑞斯托霉素刺激后的聚集正常。16 名患者的血小板中存在 αIIbβ3 受体表达缺失/减少，4 名患者的表达边界/正常。候选基因测序在 15 名患者中发现了致病性/可能致病性变异。其中 7 种变异是新的。一名受体表达缺失的患者仍然没有遗传发现。15 名患者中有 13 名（86.7%）有血缘关系，14 名患者（93.3%）为纯合子。
