Figure 1.

Patients with biallelic IRF7 variants. (A) Pedigrees of the six kindreds containing seven patients with life-threatening viral infections (P1–P7) bearing rare biallelic IRF7 variants. Solid black symbols indicate patients with critical viral infections. The IRF7 genotype is indicated under each symbol. (B) The plot depicts the population frequency of IRF7 missense and pLoF variants (gnomAD v2.1.1) against CADD score (v1.6, GRCh37). Symbols indicate a total of 463 variants, 4 identified exclusively in patients and 459 present in the gnomAD database. The patient-derived variants reported in this study are highlighted, with pLoF and missense variants colored black and red, respectively. The population-derived homozygous IRF7 missense variants are highlighted in blue. (C) Schematic representation of IRF7. The lower part represents the genomic organization of the IRF7 locus, with black rectangles indicating the exons of the gene according to different transcripts. Below, a track indicates vertebrate nucleotide conservation across the IRF7 locus. The upper part shows the primary protein domain structure of IRF7. The N-terminal portion contains an α-helical DNA binding domain, followed by domains implicated in transactivation, autoinhibition, and regulation, as indicated. The positions of the patient-derived biallelic and population-derived homozygous IRF7 variants are indicated. A blue dotted line indicates the linkage of the IRF7 K179E and Q412R variants. Hmz, homozygous; Htz, heterozygous.