The image contains multiple dot plots and pedigree charts. The pedigree charts in panels A and B illustrate the genetic and clinical status of individuals from various families with coatomer protein complex subunit alpha (C O P A) syndrome. Circles represent females, and squares represent males. Black fill indicates asymptomatic carriers. Blue, pink, green, and yellow quadrants indicate lung, joint, kidney, and skin involvement, respectively. C O P A genotypes are shown in blue, S T I N G 232 status in green, and the presence of the S T I N G H A Q haplotype in red. Diagonal bars indicate deceased individuals, and arrows indicate index cases. Open symbols represent individuals without clinical manifestations. Panel C shows a Kaplan–Meier analysis of age at symptom onset in individuals heterozygous for a coatomer protein complex subunit alpha mutation, with affected patients shown in red and unaffected individuals in blue. The y-axis represents symptom-free rate, expressed as a percentage of individuals, and the x-axis represents age in years. A significant difference is indicated with a probability value less than 0.0001. Panel D presents type one interferon pathway activation in individuals with a pathogenic coatomer protein complex subunit alpha mutation, assessed by interferon score measured by quantitative polymerase chain reaction and NanoString gene expression analysis. Patients are compared with asymptomatic carriers. Horizontal bars indicate the median. S T I N G H A Q halotype carriers are circled in black. Mann–Whitney test results are indicated with a probability value less than 0.05 and a probability value less than 0.001. Dotted lines show the upper control values of 2.466 for quantitative polymerase chain reaction and 2.724 for NanoString.
Pedigree structure, genotype, and IFN-I signalling status in familial and sporadic cases of COPA syndrome and asymptomatic COPA mutation carriers. (A and B) Pedigrees comprising both individuals manifesting COPA syndrome and clinically asymptomatic individuals (A), and sporadic cases of COPA syndrome in whom STING haplotype data were available (B). Circles and squares indicate females and males, respectively; black fill indicates clinical asymptomatic status. Blue, pink, green, and yellow quadrants indicate lung, joint, kidney, and skin involvement, respectively. COPA genotypes are shown in blue, STING 232 status in green, and presence of STING HAQ haplotype in red. Diagonal bars indicate deceased individuals. Arrows indicate index cases. (C) Kaplan–Meier analysis of age at symptom onset in individuals heterozygous for a COPA mutation (log-rank test, P < 0.0001). Affected patients are presented in salmon pink, while clinically asymptomatic individuals are presented in blue. The status of patient F3.IV.2, manifesting vitiligo in the absence of other disease features at age 18 years, was considered uncertain, so that she was not included in our further analysis. (D) IFN-I pathway activation in individuals harboring a pathogenic mutation in COPA as assessed by IFN score performed by qPCR (left panel) or NanoString (right panel). Horizontal bar indicates median. STING HAQ haplotype carriers are circled in black. Mann–Whitney test; *P < 0.05; ***P < 0.01. Dotted lines indicate the upper control values of 2.466 (qPCR) and 2.724 (NanoString).