Kazemi Ahmad, Abolghasemi Hassan, Kazemzadeh Shima, Vahidi Reza, Faranoush Mohammad, Farsinejad Alireza, Ala Fereydoun
aDepartment of Hematology, Faculty of Allied Medicine, Iran University of Medical SciencesbDepartment of Pediatrics, Baqiyatallah University of Medical Sciences, TehrancDepartment of Hematology and Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, KermandDepartment of Veterinary Sciences, Baft Branch, Islamic Azad University, BafteDepartment of Pediatric Hematology Oncology, Iran University of Medical Science, TehranfIranian Comprehensive Hemophilia Care Centre, Tehran, Iran.
Blood Coagul Fibrinolysis. 2017 Dec;28(8):681-686. doi: 10.1097/MBC.0000000000000673.
: Quantitative and/or qualitative defects of the platelet membrane glycoprotein IIb/IIIa complex lead to the clinical entity of Glanzmann's thrombasthenia. A large variety of mutations and polymorphisms are responsible for the aberrant expression and defective activity of this heterodimeric complex. The current study aimed to determine the pattern of mutations among Iranian population with Glanzmann's thrombasthenia. A total of 20 patients with Glanzmann's thrombasthenia have been evaluated. All exons and splice sites of ITGA2B and ITGB3 genes were amplified using touchdown PCR. Mutation screening was analyzed using conformation sensitive gel electrophoresis heteroduplex PCR, and DNA sequencing. In addition to finding one previously identified mutation and polymorphism, the experimenters explored 3 and 2 novel mutations and polymorphisms, respectively. One substitution mutation, two deletions of a single nucleotide, one insertion of a single nucleotide, two synonymous polymorphisms, and one missense polymorphism were found using Sanger sequencing method. All detected mutations were homozygous which will most likely contribute to the pathogenesis of Glanzmann's thrombasthenia. Furthermore, it suggested ITGB3 as the mainly affected gene impaired in the patients with Glanzmann's thrombasthenia. As expected, the molecular results were consistent with the phenotypic findings so that GPIIb/IIIa complex was disrupted due to mutations in all type-I Glanzmann's thrombasthenia patients. It is concluded that intronic alterations or epigenetic regulations could be responsible for aberrant expression and/or defective activity of GPIIb/IIIa complex among other patients.
血小板膜糖蛋白IIb/IIIa复合物的定量和/或定性缺陷导致了Glanzmann血小板无力症这一临床病症。多种突变和多态性导致了这种异二聚体复合物的异常表达和活性缺陷。本研究旨在确定伊朗Glanzmann血小板无力症患者的突变模式。共评估了20例Glanzmann血小板无力症患者。使用降落PCR扩增ITGA2B和ITGB3基因的所有外显子和剪接位点。采用构象敏感凝胶电泳、异源双链PCR和DNA测序进行突变筛查。除发现一个先前已鉴定的突变和多态性外，实验人员还分别发现了3个和2个新的突变和多态性。使用桑格测序法发现了一个替换突变、两个单核苷酸缺失、一个单核苷酸插入、两个同义多态性和一个错义多态性。所有检测到的突变均为纯合子，很可能导致Glanzmann血小板无力症的发病机制。此外，研究表明ITGB3是Glanzmann血小板无力症患者中主要受影响的受损基因。正如预期的那样，分子结果与表型结果一致，即所有I型Glanzmann血小板无力症患者的GPIIb/IIIa复合物因突变而被破坏。得出的结论是，内含子改变或表观遗传调控可能是其他患者中GPIIb/IIIa复合物异常表达和/或活性缺陷的原因。
