Figure 1: Vasculitis pathology and description of ARPC1B variants in patients.

Patient 1 (a,c) and Patient 2 (b,d) developed skin lesions associated with small vessel vasculitis. Patient 1 (a) had a complicated ulcerating lesion after a skin biopsy preceded by the more typical skin lesions seen in Patient 2 (b). Images a,b are not included in the Creative Commons license for the article. Small vessel vasculitis was confirmed by skin biopsies (c,d); arrowheads indicate: (1) epidermis, (2) dermal–epidermal junctions, (3) dermis. At low magnification (c,d, left panels) areas of leukocytoclastic vasculitis (4) were evident, which at higher magnification (c,d, right panels) showed vessel wall destruction (5) and neutrophil infiltration (6). (e) ARPC1B is located on Chromosome 7 (position numbering relative to GRCh37), immediately preceded by ARPC1A. (f) Nucleotide positions of identified mutations (black arrows) relative to ARPC1B coding exons (accession #: NM_005720.3). Patient 1 is homozygous for c.269_270dupCT, Patient 2 is homozygous for two missense variants (c.314C>T and c.712G>A). (g) ARPC1B has 6 WD40 repeat domains forming a β-propeller required for Arp2/3 complex function. The amino acid change caused by the mutation in Patient 1 causes a frame shift predicted to yield a protein lacking the last five WD40 domains; both mutations carried by Patient 2 affect WD40 domains. Adapted from http://smart.embl-heidelberg.de/smart/show_motifs.pl; ARC1B_HUMAN, O15143.