Fig 1.
SERPING1 variant on Family 1 A) Pedigree of Family 1 with persons harboring the variant c.1420C>T p.(Gln474*) and Sanger sequencing confirmation of IV,38 and IV,41.+WES and *or ** negative or positive SS respectively. B) Left, the wild-type SERPING1 protein structure with the reactive center loop (RCL) highlighted in magenta. The central beta-sheet region is indicated in red; right, SERPING1 protein structure featuring the Gln474* variant. The molecular variant promotes the insertion of the RCL into the central beta-sheet, mimicking the latent form of the protein. The absence of the RCL region is shown, and the central beta-sheet is indicated in red. The overall conformational change depicts the predicted structural transition associated with the pathogenic variant.
Fig 2.
SERPING1 variants on Family 2 and 3.
A) and B) Pedigrees of Family 2 and with persons harboring the variant c.1417G>A p.Val473Met and the Sanger Sequencing confirmation of Family 2 IV,2 and Family 3 IV,11. *or ** negative or positive SS respectively.
Fig 3.
SERPING1 variants on Family 4 A) Pedigree of Family 4 with persons harboring the variant c.1238T>G p.(Met413Arg) and the Sanger Sequencing confirmation of the Family 4 III,4..+WES and *or ** negative or positive SS respectively B) and C) DynaMut2 protein stability change predictions (ΔΔGstability) were determined by uploading the experimentally derived structure of C1-inhibitor protein to the DynaMut2 server at https://biosig.lab.uq.edu.au/dynamut2/. Dashed lines predict intramolecular interactions. Predicted hydrophobic interactions are shown in green, intramolecular clashes in pink, hydrogen bonds in orange, and carbonyl interactions in blue. (A-B) WT C1-inhibitor protein, (C-D) Met413Arg C1-inhibitor protein.
Table 1.
Clinical characteristics of patients with HAE.