The following is a summary of “Hereditary or acquired? Comprehensive genetic testing assists in stratifying angioedema patients,” published in the March 2024 issue of Allergy & Immunology by Rozevska, et al.

Hereditary angioedema (HAE) presents significant diagnostic challenges due to its episodic, non-specific symptoms and overlap with other conditions. The study focused on the genetic basis of HAE, particularly unresolved cases and those with normal C1-inhibitor levels (nC1-INH HAE). For a study, researchers sought to explore the genetic underpinnings of HAE, especially in cases where traditional diagnostic methods have failed, and to identify potential genetic variants associated with nC1-INH HAE.

The research utilized an integrative approach, employing genome, exome, and transcriptome sequencing to investigate the genetic basis of HAE. Conventional genetic testing was initially performed, identifying pathogenic variants in a subset of patients (10 out of 32). For cases where conventional methods were insufficient, advanced sequencing techniques were applied. The study included extensive genetic analysis of 21 patients with nC1-INH HAE, alongside an investigation into candidate genes for potential pathogenic variants.

Conventional testing identified pathogenic variants in 10 of the 32 patients. However, the diagnostic yield for nC1-INH HAE using advanced genetic analyses remained low, with pathogenic variants identified in only 1 of the 21 patients. Investigation into candidate genes did not reveal any pathogenic variants, leading to a re-evaluation of the patient’s diagnosis.

The study underscored the complexities and limitations of genetic testing for HAE, particularly for nC1-INH HAE. Despite employing advanced sequencing techniques, the diagnostic yield remains low, highlighting the necessity for continuous clinical assessment and re-evaluation of patients. The findings advocated for a nuanced approach to genetic testing and emphasized the need for further research to understand the genetic landscape of nC1-INH HAE comprehensively. The study contributed valuable insights into the genetic intricacies of HAE, emphasizing the importance of advanced sequencing and integrated diagnostic strategies in unraveling the complexities of the disease.

Reference: aacijournal.biomedcentral.com/articles/10.1186/s13223-024-00889-5