Genetic Testing for Hereditary and Recurrent Angioedema

Virant Diagnostics offers clinically directed genetic testing for hereditary angioedema and related forms of recurrent swelling. Testing options include SERPING1 testing, HAE-nC1INH gene testing, targeted familial variant testing, HAE panels, broader angioedema panels, and whole exome sequencing. Results should be interpreted together with the patient’s symptoms, family history, complement/C1 inhibitor testing, and clinical evaluation.

SERPING1 Testing for HAE with C1 Inhibitor Deficiency

The SERPING1 gene is associated with hereditary angioedema due to C1 inhibitor deficiency or dysfunction.

Available testing includes:

Sequencing of the SERPING1 (OMIM 106100) coding region, including ±10 base pairs for exons 2–8
SERPING1 exon 1–8 duplication/deletion testing

This testing may be considered when hereditary angioedema type I or type II is suspected based on clinical history and complement/C1 inhibitor testing.

HAE with Normal C1 Inhibitor Testing

Some patients have clinical features of hereditary angioedema but normal C1 inhibitor level and function. This condition is often referred to as HAE with normal C1 inhibitor, or HAE-nC1INH.

Virant Diagnostics offers testing for known HAE-related variants in the following genes:

F12
KNG1
ANGPT1
PLG
MYOF
HS3ST6

Available testing may include sequencing for known HAE-related variants and F12 duplication/deletion testing for exons 1–12, except exon 3.

Targeted Familial Variant Testing

Targeted testing may be appropriate when a specific disease-associated variant has already been identified in a family member or through prior testing.

Targeted testing may include:

Testing for a known SERPING1 coding variant
Testing for a known HAE-nC1INH variant listed in Virant’s HAE-related gene table
Clinical confirmation of a variant previously identified in a research laboratory

This approach may help clarify whether relatives carry a known familial variant.

Hereditary Angioedema Panel Options

Panel testing allows multiple HAE-related genes to be evaluated at the same time. The best panel depends on the patient’s clinical history, complement/C1 inhibitor results, family history, and prior genetic findings.

Panel	Genes Included	Additional Testing Included
HAE-nC1INH Panel	F12, KNG1, ANGPT1, PLG, MYOF, HS3ST6	Sequencing of known HAE-related variants; F12 duplication/deletion testing for exons 1–12, except exon 3
HAE Panel	SERPING1, F12, KNG1, ANGPT1, PLG, MYOF, HS3ST6	SERPING1 sequencing and duplication/deletion testing; sequencing of known HAE-nC1INH variants; F12 duplication/deletion testing
4-Gene HAE Panel I	SERPING1, F12, KNG1, ANGPT1	SERPING1 duplication/deletion testing; F12 duplication/deletion testing for exons 1–12, except exon 3
4-Gene HAE Panel II	SERPING1, PLG, MYOF, HS3ST6	SERPING1 duplication/deletion testing

Expanded Clinical Angioedema Genetic Testing

In selected cases, broader genetic testing may be considered when the clinical picture suggests hereditary or recurrent angioedema but standard HAE testing does not fully explain the patient’s symptoms.

Angioedema Gene Panel

The Angioedema Gene Panel sequences and analyzes 77 genes involved in complement, coagulation, and tissue kallikrein pathways.

This expanded clinical panel may be useful when a healthcare provider is evaluating a broader differential diagnosis for recurrent angioedema, unexplained swelling episodes, or suspected inherited disorders involving angioedema-related pathways.

Click here for details and descriptions for each gene on the panel.

Whole Exome Sequencing

Whole exome sequencing may be considered when a broader genetic evaluation is needed, especially when a patient’s symptoms or family history suggest a possible inherited condition that is not explained by targeted HAE or angioedema panel testing.

References

Click here for references.