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. 2022 Mar 15;132(6):e128808. doi: 10.1172/JCI128808

Figure 1. A synonymous exonic mutation and 2 intronic splice donor mutations mediate alternative splicing of IKBKG and lead to severe autoinflammatory disease.

Figure 1

(A) Pedigree and clinical features of developmental and inflammatory diseases in patients P1–P3. (B) Schema of mutations identified in patients P1–P3 and other NEMO mutants. Note exon coloring used for C and D. Patient P4 has the well-described NEMO-C417R zinc finger hypomorphic mutation. I DNA gel electrophoresis of IKBKG cDNA from P1, P2, P3, and healthy control (HC) dermal fibroblasts. Chromatograms of Sanger-sequenced FL isoforms from P1 and HCs and the variant isoform from P1–P3. (D) Schema of minigene spanning IKBKG exons 4–6 containing the reference sequence or patient mutations. DNA electrophoresis of cDNA and sequence traces are shown as In C. The 574 bp fragment contains noncoding intronic sequence in addition to a fragment of exon 5. WT = IKBKG minigene containing reference sequence. (E) Western blot of NEMO from patients P1–P3 and NEMO control patient skin fibroblasts, optical densitometry of FL-NEMO relative to loading control is shown in red, of NEMO-Δex5 in blue. (F) Western blot of PBMCs and whole cell lysate from patients P1, P2, and P3 and 2 healthy controls (HCs).