Severe course of HAE and a new variant of the SERPING1 gene in a large Caucasian family

Abstract

Introduction. Hereditary angioedema (HAE) is a primary immunodeficiency with a defect in the complement system, which can be accompanied by severe life-threatening clinical symptoms in the form of abdominal attacks and angioedema. This article presents details of the study, follow-up, and treatment of a large Karachai family in which 10 people had suspected type I HAE.

Aim – identification of a mutation in the SERPING1 gene encoding C1-INH in family members with identical symptoms.

Material and methods. Eight people with angioedema and abdominal attacks were included in the study. Direct Sanger sequencing was performed based on the complaints, examination, and tests of the family members’ blood samples (changes in C4 level, C1-INH concentration and functional activity of C1-INH). At the same time objective assessment of HAE symptoms severity was performed using validated questionnaires.

Results. For the first time a new variant c.1127_1130dup [p.(Val378Phefs*48)] in the heterozygous state was detected in exon 7 of the SERPING1 gene in all patients. It is cosegregating with deficient levels and activity of C1-INH.

Conclusion. The obtained data extend the understanding of new mutation variants in the gene encoding C1-INH (SERPING1) out of more than 700 already known mutations that can lead to a decrease in protein synthesis or its functional insufficiency. Identification of mutations in the SERPING1 gene can reduce the waiting period for a patient to be diagnosed with HAE.

Keywords:primary immunodeficiency; hereditary angioedema; mutation; SERPING1; lanadelumab

For citation: Ukhanova O.P., Budnikov P.V., Podsvirova S.S., Palagota D.S. Severe course of HAE and a new variant of the SERPING1 gene in a large Caucasian family. Immunologiya. 2023; 44 (1): 103–8. DOI: https://doi.org/10.33029/0206-4952-2023-44-1-103-108 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

Authors’ contribution. The concept of the study – Ukhanova O.P.; material collection and processing – Podsvirova S.S., Palagota D.S., Budnikov P.V.; text writing – Ukhanova O.P.; text editing – Budnikov P.V.

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