Novel hereditary angioedema linked with a heparan sulfate 3-O-sulfotransferase 6 gene mutation

BackgroundHereditary angioedema (HAE) is a potentially fatal disorder resulting in recurrent attacks of severe swelling. It may be associated with genetic deficiency functional C1 inhibitor or normal (HAEnCI). In families HAEnCI, HAE-linked mutations the F12, PLG, KNG1, ANGPT1, MYOF genes have been identified. many HAEnCI cause disease currently unknown.ObjectiveThe aim this study was to identify novel disease-linked mutation for HAEnCI.MethodsThe methods comprised whole exome sequencing, Sanger sequencing analysis, pedigree bioinformatic analysis mutation, and biochemical parameters kallikrein-kinin (contact) system.ResultsBy performing on multigenerational family we were able heparan sulfate (HS)-glucosamine 3-O-sulfotransferase 6 (HS3ST6) c.430A>T (p.Thr144Ser) all 3 affected members who sequenced. This gene encodes HS-glucosamine (3-OST-6), which involved last step HS biosynthesis. The p.Thr144Ser likely affect interaction between 2 ?-sheets stabilizing active center 3-OST-6 protein.ConclusionsWe conclude that mutant fails transfer sulfo groups 3-OH position HS, incomplete affects cell surface interactions key players formation mechanism development. Hereditary unknown. HAEnCI. system. By protein. We