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

Background Hereditary angioedema (HAE) is a potentially fatal disorder resulting in recurrent attacks of severe swelling. It may be associated with a genetic deficiency of functional C1 inhibitor or with normal C1 inhibitor (HAEnCI). In families with HAEnCI, HAE-linked mutations in the F12, PLG, KNG1, ANGPT1, or MYOF genes have been identified. In many families with HAEnCI the genetic cause of the disease is currently unknown. Objective The aim of this study was to identify a novel disease-linked mutation for HAEnCI. Methods The study methods comprised whole exome sequencing, Sanger sequencing analysis, pedigree analysis, bioinformatic analysis of the mutation, and biochemical analysis of p…

On the pathogenicity of the plasminogen K330E mutation for hereditary angioedema

Hereditary angioedema with a mutation in the plasminogen gene

Background Hereditary angioedema (HAE) with normal C1-INH (HAEnCI) may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or functional mutations in other genes that are still unknown. We sought to identify and characterize a hitherto unknown type of HAE with normal C1-INH and without mutation in the F12 gene. Methods The study comprised analysis of whole-exome sequencing, Sanger sequencing, and clinical data of patients. Results We detected a mutation in the plasminogen (PLG) gene in patients with HAEnCI. The mutation c.9886A>G was located in exon 9 leading to the missense mutation p.Lys330Glu (K330E) in the kringle 3 domain of the PLG protein. The mutation…

Hereditary angioedema cosegregating with a novel kininogen 1 gene mutation changing the N‐terminal cleavage site of bradykinin