Genetics and pedigrees of families with IKZF1 mutations. (A) Segregation of the IKZF1 mutations and clinical and immunological phenotypes. Squares and circles indicate male and female family members, respectively. Question mark indicates an unscreened individual. (B) Schematic presentation of the structure of IKAROS isoform 1 (NM_006060). Dark gray indicates ZFs, and arrows indicate the site of the mutations. Numbers indicate amino acid location. Previously reported germline IKAROS mutations in CVID or CID patients are indicated below the domain. Blue color indicates haploinsufficient mutations (DNA binding–defective mutations and loss of 1 IKZF1 allele); DN mutations are shown in red; dimerization defective–mutations are shown in green; and gray color indicates the variants whose functions are unclear. (C) Sequence conservation of ZF5 and ZF6 in IKAROS. The mutated amino acid sites found in families C and D (C467 and R502, respectively) are enclosed in the green box.