Hereditary angioedema in a single family with specific mutations in both plasminogen and SERPING1 genes.

Background: Hereditary angioedema (HAE) is a group of genetic diseases characterized by recurrent, painful and potentially lethal tissue swelling. The most common form results from mutations in the SERPING1 gene, leading to reduced function of complement 1 inhibitor (C1-INH). Rarer forms with normal C1-INH may arise from mutations in the coagulation factor F12 gene, but mostly the genetic background is unknown. Recently, a novel HAE mutation in the plasminogen (PLG) gene was shown.

Patients And Methods: We analyzed the various clinical manifestations of HAE in 14 related patients using clinical data, biochemical analysis for C1-INH and C4 as well as gene sequencing.

Results: Patients' symptoms were assigned to two different forms of HAE. In ten patients suffering from swelling of the lips or tongue but not of the extremities, a mutation in the PLG gene (c.988A>G) was found whereas in the only four patients with swelling of the gastrointestinal tract and extremities, a mutation in the SERPING1 gene (c.1480C>T) was identified. In two cases this was additional to PLG c.988A>G.

Conclusions: This unique finding of two different HAE-specific mutations in a large family not only explains the divergent phenotypes but also supports a genotype-phenotype correlation showing that abdominal attacks and swelling of the extremities are common with HAE-C1-INH but unusual with HAE-PLG.