Molecular genetic diagnosis of hereditary angioedema

Hereditary angioedema (HAE) is a rare genetic condition currently subdivided into two groups: HAE due to C1-inhibitor deficiency (Type I) or dysfunction (Type II) (C1-INH-HAE) and HAE with normal activity of C1‐INH (nC1- INH-HAE). C1-INH-HAE is estimated to occur in approximately 99 % of cases HAE and is caused by sequence variants in the SERPING1 gene. The prevalence of nC1-INH-HAE is extremely low and accounts for about 1 % of all cases of HAE. nC1-INH-HAE currently subdivided on HAE, due to mutations in factor XII (FXII-HAE), plasminogen (PLG-HAE), angiopoietin 1 (ANGPT1-HAE), kininogen 1 gene (KNG1-HAE), or angioedema of unknown origin (U-HAE).

The amplicons of the entire coding regions and splice-sites of 18 genes from 24 patients (18 female) belonging to 17 families were analyzed by Next Generation Sequencing (NGS). The median age of patients was 33.5, of onset ‒ 16 years. 15 patients had a family history of edema.

We identified seven C1-INH-HAE patients and variants were detected in the SERPING1 gene. For three patients (members of the same family), a heterozygous variant was found deep in the intron of the SERPING1 gene, which is likely to affect protein synthesis. We identified two patients with changes in the PLAUR gene, which may be associated with the manifestation of symptoms angioedema. Six patients showed abnormalities in the genes AGT and KNG1, which can probably explain their early hypertension, which could provoke the appearance of edema.

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