Fig. 1: Identification of a biallelic TNF variant in two patients with pulmonary TB.
From: Tuberculosis in otherwise healthy adults with inherited TNF deficiency
a, Pedigree of two related kindreds showing familial segregation of the c.190_191ins20 (p.P64Lfs*13) TNF allele. Each generation is designated by a Roman numeral. Male and female individuals are represented by squares and circles, respectively. The filled boxes indicate individuals affected by TB and the crossed symbols indicate deceased individuals. ‘E?’ indicates an unknown TNF genotype. Red ‘M’ indicates the variant allele. The triangles indicate spontaneous abortion and the diamond indicates the death of an individual of unknown sex. b, Chest contrasted CT scan showing the pulmonary lesions of P1. c, Ziehl–Neelsen staining of a pulmonary biopsy specimen from P1 showing acid-fast bacilli (arrow). Data shown are representative of one independent experiment. d, Haematoxylin and eosin staining of a granuloma from P1 at different magnifications. Data shown are representative of one independent experiment. Scale bars, 2 mm, 200 µm and 50 µm (from left to right). e, Immunohistochemical staining for CD3, CD4 and CD8, indicating the presence of T cells within the granuloma of P1. Data shown are representative of one independent experiment. Scale bars, 200 µm. f, Schematic of the full-length and cleaved TNF proteins, with the intracellular (IC), transmembrane (TM) and extracellular (EC) domains indicated. The red part of the mutant TNF protein (P64Lfs*13) corresponds to the amino acids inserted due to the frameshift variant. aa, amino acids. N term. and C term., N-terminal and C-terminal fragments. g, The minor allele frequency (MAF; gnomAD, v.2.1.1) and combined annotation-dependent depletion (CADD; v.1.6) score for biallelic non-synonymous TNF variants reported in gnomAD v.2.1.1 or found in P1 and P2. The MSC is indicated by a dotted line.
