To report on nontargeted whole-exome sequencing (WES) studies that describe genetic variants associated with severe bacterial infection (SBI) susceptibility in previously healthy patients without known predispositions for infections.
Key Findings:
Twelve studies included, with 694 patients analyzed using WES.
42% of previously healthy patients with SBI had putatively disease-causing variants in genes related to inborn errors of immunity, highlighting the need for further investigation.
Diverse methods used for prioritizing genetic variants led to the identification of different genes/pathways associated with infection susceptibility.
Interpretation:
The findings support the utility of WES as a diagnostic tool for identifying genetic factors contributing to SBI in previously healthy individuals, potentially guiding future therapeutic strategies.
Limitations:
Heterogeneity in study designs and methods prevented meta-analysis, complicating the interpretation of results.
Limited sample sizes due to the rarity of severe bacterial infections.
Conclusion:
WES is a promising approach for diagnosing inborn errors of immunity in SBI patients, but future studies should adhere to strict guidelines for variant prioritization, such as standardized criteria for variant classification, and consider collaborative efforts for larger sample sizes.
