PIK3CD and Immunodeficiency: In contrast to SHORT syndrome, mutations in the inter-SH2 domain of PIK3R1, mostly leading to skipping of exon 11, were shown in 2014 to activate PI3K in vitro and to cause immunodeficiency (APDS2) (Deau et al., 2014; Lucas et al., 2014b) similar to that caused by activating mutations in p110δ (APDS1) (Angulo et al., 2013; Lucas et al., 2014a).