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

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.

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.

All probands were diagnosed with HAE type 1. Nine mutations were found in nine patients: c.44delT, c.289C

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.