PIK3CD and hyperinsulinemic hypoglycemia, familial, 4: Both defects lead to primary immunodeficiency, and NK cell number in the patient reported with p85α deficiency was significantly decreased when compared to healthy ranges (70).What have emerged as a much more common variation are GOF muta-tions in PIK3CD or PIK3R1. PIK3CD GOF mutations were independently reported in 2014 by Lucas et al. (65) and Angulo et al. (114) and lead to hyperactivation of PI3K110δ signaling by interrupting the interaction between PI3K110δ and the p85α-regulatory subunit, or by constitutive membrane association and activation (65, 114, 115).