Hereditary angioedema caused by a premature stop codon mutation in the SERPING1 gene.

Background: Hereditary angioedema with deficient and dysfunctional C1 inhibitor (C1-INH-HAE) is a rare genetic disorder. The majority of the cases with this disease are caused by mutations in the C1-inbitor gene SERPING1 and are classified as type 1 and type 2. We aimed to detect mutations in the SERPING1 gene and evaluate its expression in nine probands with hereditary angioedema from nine different families.

Methods: Nine probands with hereditary angioedema from nine different families and 53 healthy controls were recruited in this study. All eight exons and intron-exon boundaries in the SERPING1 gene were amplified by PCR and then sequenced. Mutations were identified by alignment with reference sequences. mRNA expression was measured by real-time PCR.

Results: All probands were diagnosed with HAE type 1. Nine mutations were found in nine patients: c.44delT, c.289C
Conclusions: Three known and six novel mutations in the SERPING1 gene were identified, and they produced a truncated nonfunctional C1 inhibitor without a reactive central loop. All the mutations led to reduced expression of SERPING1 mRNA in peripheral blood and low antigenic C1 inhibitor levels.