Many of the lessons of the genomics revolution are common across rare diseases and apply equally to inborn errors of immunity (IEIs). However, the immune system has specific characteristics that impact the effects and the interpretation of genetic variation. This includes the high background rates of polygenic autoimmune disease and sporadic infection, which reduce the pre-test probability of identifying a monogenic cause of immune disease in any given patient. Additionally, the plasticity of bone marrow allows for unusual effects of somatic variation compared to more topographically defined organs, while there are increasing numbers of immune phenocopies of IEI. This presentation will attempt to guide the listener through the general rules of confirming disease-association of genetic variants and how these differ with diagnosing IEIs.
Paul Gray (Sun,) studied this question.