LIG4 and severe combined immunodeficiency: Pathogenic mutations in genes that encode for proteins implicated in V(D)J recombination (23), such as mutations in RAG1) and RAG2 (24), DCLRE1C (11, 25), PRKDC (26, 27) and LIG4 (28, 29), typically cause T-B-NK+ SCID and together account for approximately 20-25% of all SCID.