RNF168 and Immunodeficiency: Functionally, bi-allelic heterozygous nonsense mutations in the gene encoding RNF168 cause RIDDLE syndrome (radiosensitivity, immunodeficiency, dysmorphic features and learning difficulties) [127,138] and depletion of either RNF8 or RNF168 in cells causes hypersensitivity to DSB inducing agents.