Identification of potential pathogenic genes for severe aplastic anemia by whole‐exome sequencing

Background Severe aplastic anemia (SAA) is a syndrome of severe bone marrow failure due to hyperfunction of CD8+ T cells. While, the genetic background of SAA is still unknown. In this study, we tried to explore the possible genetic variants in CD8+ T cells of SAA patients. Methods We performed whole‐exome sequencing (WES) in CD8+ T cells of 4 SAA patients and 7 normal controls. The mutations that existed in SAA but not in NCs were identified as candidate genes. Then, we compared them with genes in the enriched KEGG pathway of differently expressed genes (DEGs) from previous RNA‐seq. After analyzing the types of mutations, we identified possible pathogenic genes and validated them by RT‐PCR. Finally, we compared them with the autoimmune disease‐related genes in DisGeNET database to select the most possible pathogenic genes. Results We found 95 candidate mutant genes in which, 4 possible pathogenic genes were identified: PRSS1, KCNJ18, PRSS2, and DGKK. RT‐PCR results showed that compared with NCs, PRSS1 and KCNJ18 mRNA expression was significantly increased in SAA patients (p