PAX5 and hereditary disease: The contribution of germline genetic variants to ALL risk is now well established, particularly through genome-wide association studies.10-16 However, the susceptibility conferred by these common variants is usually modest (1.5-2-time increase in ALL risk for each copy of the variant allele).50 In contrast, a smattering of congenital genetic disorders have been linked to ALL predisposition (e.g., PAX5,21SH2B322 and TP5323 germline mutations), resulting in a dramatic increase in disease risk.