Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Medina, Saudi Arabia.
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Hematol Oncol Stem Cell Ther. 2022 Mar 1;15(1):21-26. doi: 10.1016/j.hemonc.2021.01.003.
Glanzmann's thrombasthenia (GT) is an autosomal recessive congenital bleeding disorder of platelet aggregation. Mutations in ITGA2B and ITGB3 genes result in quantitative and/or qualitative abnormalities of the glycoprotein receptor complex IIb/IIIa (integrin αIIbβ3), which in turn impairs platelet aggregation and lead to GT. In this study, whole genome single nucleotide polymorphism (SNP) genotyping as well as whole exome sequencing was performed in a large family segregating GT. Analysis of the genotypes localized the disease region to chromosome 17q21.2-q21.3. Filtration of whole exome data and candidate variants prioritization identified a pathogenic variant in the ITGB3 gene. The single nucleotide deletion variant (c.2113delC) in exon 13 of the ITGB3 gene is predicted to cause a frameshift and absence of vital C-terminal domains including the transmembrane helix and the cytoplasmic domain. Clinical variability of the bleeding phenotype in affected individuals with the same mutation suggests that other genetic and nongenetic factors are responsible for determining GT features.
血小板无力症（GT）是一种常染色体隐性遗传性血小板聚集障碍的先天性出血性疾病。ITGA2B 和 ITGB3 基因突变导致糖蛋白受体复合物 IIb/IIIa（整合素 αIIbβ3）的数量和/或质量异常，进而损害血小板聚集并导致 GT。在这项研究中，对一个分离 GT 的大型家族进行了全基因组单核苷酸多态性（SNP）基因分型和全外显子组测序。基因型分析将疾病区域定位在染色体 17q21.2-q21.3。全外显子组数据的筛选和候选变异优先级确定了 ITGB3 基因中的致病性变异。ITGB3 基因外显子 13 中的单核苷酸缺失变异（c.2113delC）预计会导致移码和重要的 C 末端结构域缺失，包括跨膜螺旋和细胞质结构域。具有相同突变的受影响个体的出血表型的临床变异性表明，其他遗传和非遗传因素决定了 GT 的特征。
