PMC6221951_01
Family tree and Sanger sequencing results. (A) Family tree showing affected and unaffected members enrolled in the study; segregation of the p.R1042G mutation in C3 with disease is also indicated. Arrow indicates the index case. (B) Sanger sequencing confirmed a heterozygous C/G mutation (blue/black overlapping line) at position c.C3124 of C3 gene in family members II-1, I-1, and II-2 that is absent (single blue line corresponding to wild type "C" allele) in I-2 and II-3.
fimmu-09-02524-g0001.jpg
PMC6221951_01_fimmu-09-02524-g0001.jpg
F1
The index case was a previously well 6-year-old male, born to non-consanguineous Caucasian parents (family tree, Figure 1A). This revealed a heterozygous c.3124C>G (p.R1042G) variant in exon 24 of C3 gene, which was confirmed by Sanger sequencing (Figure 1B). I-1 and absent in I-2 and II-3 (Figures 1A,B). Interestingly I-1 subsequently developed recurrent cutaneous vasculitis (purpuric rashes) and arthralgia (Figure 2F) with no documented renal abnormalities and required corticosteroid therapy. II-2 was also reporting long standing history of recurrent fingertip erythema with no other systemic symptoms while I-2 and II-3 were asymptomatic (see Supplemental Table 2 for other laboratory tests for I-1 and II-2).
Cutaneous vasculitis and digital ischaemia associated with heterozygous gain-of-function mutation in C3. (A-C). Discolouration and erythema in fingers of both hands and toes of the index case (II-1). (D,E). Digital ischaemic necrosis seen in the second and third digit of the left foot for II-1. (F) Cutaneous vasculitis affecting I-1.
fimmu-09-02524-g0002.jpg
PMC6221951_01_fimmu-09-02524-g0002.jpg
F2
He spontaneously developed acute, painful erythema and discoloration of his fingers and toes (Figures 2A-C). He rapidly deteriorated over the next 48 h, developing critical digital ischaemia of his toes (Figures 2D,E). I-1 and absent in I-2 and II-3 (Figures 1A,B). Interestingly I-1 subsequently developed recurrent cutaneous vasculitis (purpuric rashes) and arthralgia (Figure 2F) with no documented renal abnormalities and required corticosteroid therapy. II-2 was also reporting long standing history of recurrent fingertip erythema with no other systemic symptoms while I-2 and II-3 were asymptomatic (see Supplemental Table 2 for other laboratory tests for I-1 and II-2).