Pedigree, clinical manifestations, and mutations of a patient with immunodeficiency. (A) Pedigree of the family; “wt” indicates a wt genotype for CHUK, E? indicates that we don’t have the genotype of this family member. (B) Aspect of primary pulmonary lymphoma on the CT scan: consolidation of the lower two-thirds of the left lung (asterisk) with the invasion of the mediastinum, infiltration of the left pulmonary artery (white arrowhead), and complete thrombosis of the left pulmonary veins (white arrow). Thickening of the interlobular septa in the remainder of the ventilated lung, consistent with venous stasis or carcinomatous lymphangitis (black arrowhead). No normal lymph nodes or adenomegaly were individualized in the mediastinum or in the pulmonary hilum. A few small lymph nodes were visible in the axillary areas. The PET-CDFDG 18F performed within 48 h showed hypermetabolism of the lesions and in three coeliomesenteric lymphadenopathies (black arrows). (C) Localization of the mutation on the protein sequence of IKKα. The patient mutations are shown in red, while previously in vitro validated reported variants are in gray. (D) Sanger sequencing of RT-PCR products (cDNA) from the indicated cells. (E) Combined annotation-dependent depletion score versus minor allele frequency (CADD-MAF) (left panel) and polyphen score versus MAF (right panel). The patient variants are in red and dark red, and the other gnomAD variants are in gray. MSC: mean significance cutoff for CHUK CADD score (3.13). (F) Protein expression of IKKα and IKKγ οn protein lysates from healthy controls SV40-fibroblasts and the patient (P, in red). GAPDH was used as a protein loading control. (G) Protein expression of HA-tagged IKKα on protein lysates from transfected HEK293T cells with the different variants, the wt, or an EV. The patient variants are displayed in red. Source data are available for this figure: SourceData F1.