The following is a summary of “Hereditary angioedema with normal C1 inhibitor associated with carboxypeptidase N deficiency,” published in the May 2024 issue of Allergy & Immunology by Vincent, et al.
Hereditary angioedema (HAE) is a potentially life-threatening condition marked by recurrent episodes of subcutaneous or submucosal swelling. HAE with normal C1 inhibitor (HAE-nC1-INH) is often underdiagnosed. While genetic variants have been linked to HAE-nC1-INH in some families, the genetic causes remain unknown for many patients. The role of genes involved in bradykinin catabolism in HAE-nC1-INH has yet to be fully understood. For a study, researchers sought to investigate the biological parameters and genes related to the kallikrein-kinin system in families exhibiting a clinical phenotype of HAE-nC1-INH and carboxypeptidase N (CPN) deficiency.
The study included four families with HAE-nC1-INH and CPN deficiency. Clinical records of the patients were reviewed, biological parameters of the kallikrein-kinin system were measured, and genetic analysis was conducted using next-generation sequencing and Sanger sequencing. Predictive algorithms (Human Splicing Finder, Sorting Intolerant From Tolerant, Polymorphism Phenotyping v2, MutationTaster, and ClinPred) were utilized to classify genetic variants as affecting splicing, benign, deleterious, or disease-causing.
Patients experienced angioedema and urticaria, primarily on the face/lips, and some reported abdominal pain or laryngeal symptoms. Affected individuals showed low CPN activity, ranging from 30% to 50% of the median plasma value. Three variants of the CPN1 gene, which encodes the catalytic 55-kDa subunit of CPN, were identified: c.533G>A, c.582A>G, and c.734C>T. CPN deficiency, associated with these genetic variants, was observed to co-segregate with HAE-nC1-INH symptoms in affected family members.
Variants in the CPN1 gene are associated with CPN deficiency and HAE-nC1-INH symptoms in four unrelated families. Genetic CPN deficiency may lead to the accumulation of bradykinin and anaphylatoxins, contributing synergistically to angioedema and urticarial symptoms.
Reference: jaci-global.org/article/S2772-8293(24)00019-5/fulltext
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