Primary immunodeficiency (PID) is characterised by recurrent and often life-threatening infections, autoimmunity and cancer, and it presents major diagnostic and therapeutic challenges. Although the most severe forms present in early childhood, the majority of patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation. Consequently, in sporadic PID genetic diagnosis is difficult and the role of genetics is not well defined. We have addressed this by performing whole genome sequencing of a large cohort of PID patients. This analysis has identified new genes contributing to PID and deepened our understanding of the key pathways determining variation in human immune responsiveness.
