Genetic causes of primary immunodeficiency in Jordanian population.

Ιnborn errors of immunity (IEI), represent a heterogenous collection of > 480 immune system anomalies, leading to severe infections, autoimmune disorders, and malignancies. While these conditions are rare globally, their prevalence is notably higher in the Jordanian population, attributed to elevated rates of consanguinity. The intricate nature of IEI has driven the adoption of genomic technologies for the identification of associated genetic defects. Here, we employed whole-exome sequencing on nine Jordanian IEI patient samples, confirming germline single-nucleotide variations (SNVs) in 14 genes through Sanger sequencing. Of note, STAT1, ELANE and IFIH1 harbored mutations that were previously unreported in the Jordanian IEI population. In addition, mutations in CARMIL2 (c.3683C>T), TNIP1 (c.460C>G), and STAT1 (c.1061T>C) were confirmed, marking their association with Jordanian IEI. For robustness, the genomic databases Ensemble, Genome AD, and ClinVar were used to confirm the SNVs' associations with IEI. KEGG pathway analysis also showed involvement of the IL-17 signaling pathway (IL17RA), Th17 cell differentiation (STAT1), JAK-STAT signaling pathway (STAT2 and TYK2), neutrophil extracellular trap (NET) formation (ELANE), cocaine addiction (GPSM1), and cytokine-cytokine receptor interaction (IL17RC). In summary, our findings reveal the association of novel STAT1, ELANE and IFIH1 mutations, as well as known mutations in NLRP12, GPSM1 and TNIP1 in the Jordanian context of IEI.