Figure 1.

Clinical features and identification of PSMB10 de novo missense variants

(A) PSMB10 variants in six infants with SCID.

(B) Erythematosquamous rash in individual 1 at 12 weeks after birth.

(C) Histology of the initial skin biopsy of individual 1 showed a graft-versus-host-disease-like pattern with vacuolar interface inflammation, multiple scattered apoptotic keratinocytes, and involvement of the adnexal structures, in the presence of a limited lymphocytic infiltrate (hematoxylin and eosin staining; original magnification ×41).

(D) Histopathological evaluation of an inguinal lymph node extracted from individual 5 showed a paucicellular, stroma-rich lymph node.

(E) A jejunal biopsy from individual 3 was hallmarked by partial villous atrophy and crypt hyperplasia with relatively few lymphocytes.

(F) Colonic mucosa biopsied from individual 5 showed preserved crypt architecture with an empty lamina propria with few lymphocytes, in keeping with an immunodeficiency-related enteropathy.

(G) Immunohistochemistry showed the absence of CD3⁺ and CD20⁺ positive cells in the colon samples from individual 5, although significant numbers of CD4⁺ cells were observed that may be of a macrophage/monocyte lineage.

(H) Visualization of the three identified PSMB10 variants at the cDNA and protein level. The conservation across species is shown and scaled by color. The asterisk indicates the position of a previously studied Psmb10 variant in TUB6 mice.

(I) Immunoblot for PSMB10 in dermal fibroblasts of 3 controls, individual 3 (F3.II.1; p.Gly201Arg), individual 4 (F4.II.1; p.Gly201Arg), and individual 5 (F5.II.1; p.Asp56His), with or without prior IFN-gamma induction. Upper band (white arrowhead) represents immature and lower band (black arrowhead), mature, PSMB10; subject samples also show an additional, intermediate band (black arrow). Representative of 4 independent experiments.