Advancing Genomics in Inborn Errors of Immunity Through Functional Assessment of Immune Signalling Pathways

The majority of patients diagnosed with inherited diseases of immune impairment are genetically unsolved, impeding use of targeted therapeutics. This thesis describes the development and utilisation of a genomics analysis pipeline to aid in selection of potentially causal genetic variants from the many gene variants in an individual. Alongside, functional assessment of immune signalling pathways, the thesis demonstrates the benefits of a pathway-focused, function-first approach for identification of candidate genetic variants in patients with previously inconclusive genomic analysis. This function-first approach may fast track identification of candidate variants, and should be considered in the diagnosis of other elusive genetic conditions.