Gene mutations in members of the PI3K/Akt signalling pathway are related to immune thrombocytopenia pathogenesis

Purpose Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. In this research, we conducted an in-depth genomic analysis of a cohort of patients and elucidated the molecular features associated with the pathogenesis of ITP. Method High-molecular-weight genomic DNA was extracted from freshly frozen bone marrow blood mononuclear cells (BMBMCs) from 20 active ITP patients. Next, the samples were subjected to molecular genetic analysis by whole-exome sequencing (WES), and the results were confirmed by Sanger sequencing. The signalling pathways and cellular processes associated with the mutated genes were identified with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Results The results of this study revealed 3,998 missense mutations involving 2,269 genes in more than 10 individuals. Some unique genetic variants, including phosphatase and tensin homologue (PTEN), insulin receptor (INSR) and coagulation factor C homology (COCH) variants, were the most associated with the pathogenesis of ITP. Functional analysis revealed that these gene mutations mainly affected the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signalling pathways (signal transduction) and platelet activation (immune system). Conclusions Our findings demonstrate the functional connections between these gene variants and ITP. Although the underlying mechanisms and the impact of these genetic variants remain to be revealed through further investigation, the application of next-generation sequencing in ITP in this paper is valuable for revealing the genetic mechanisms of ITP. Summary Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. DNA mutation profile of ITP patient bone marrow samples (n=20) were investigated by using next-generation sequencing (NGS), and then confirmed by sanger sequencing method. Our results showed PTEN, INSR and COCH were mutated in all ITP patients. Functional analysis revealed these mutation genes mainly participate PI3K/Akt signaling pathways and platelet activation. These results suggest that genetic alterations might be involved in the pathogenesis of ITP.