Primary immunodeficiencies: novel genes and unusual presentations

Abstract

Abstract Recent advances in genomics have greatly expanded the spectrum of primary immune deficiencies (PIDs). Along with the identification of pathogenic variants in novel genes, distinct phenotypes have been associated with different variants in the same gene. Although PIDs have been historically defined based on increased susceptibility to infections, immune dysregulation has emerged as a frequent and in some cases, predominant phenotype. Autoimmune cytopenias with onset in childhood, lasting longer than 12 months, and affecting multiple lineages should raise the suspicion of a possible PID with monogenic origin. Characterization of the various molecular and cellular mechanisms responsible for these unusual manifestations of PIDs, although at times resource intensive, may allow for targeted intervention in many of them.