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Test Code GNANG Hereditary Angioedema Focused Gene Panel, Next-Generation Sequencing, Varies


Ordering Guidance


This test is designed to detect disease-causing variants in the F12, KNG1, and PLG genes and to be utilized for genetic confirmation of a clinical diagnosis of hereditary angioedema with normal C1 inhibitor (HAE with normal C1INH) or factor XII deficiency.

 

Genetic testing for HAE with normal C1INH should only be considered if there is a documented family history of angioedema that does not respond to chronic, high-dose antihistamine therapy, normal complement studies, normal C1-INH level and function, and no exposure to medications that could cause angioedema, such as angiotensin-converting enzyme inhibitors or nonsteroidal anti-inflammatory drugs.

 

Genetic testing for factor XII deficiency should only be considered if clinical and family history, initial coagulation screens, or initial activity tests indicate a diagnosis.

 

This test does not measure complement 4, C1INH antigen, C1INH functional, or factor XII activity levels.

-For assessment of C4, order C4 / Complement C4, Serum.

-For assessment of C1INH antigen, order C1ES / C1 Esterase Inhibitor Antigen, Serum.

-For assessment of functional C1INH , order C1INF / C1 Esterase Inhibitor, Functional, Serum.

-For assessment of factor XII activity, order F_12 / Coagulation Factor XII Activity Assay, Plasma.

 

Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

 

Targeted testing for familial variants (also called site-specific or known variants testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Necessary Information


Rare Coagulation Disorder Patient Information is required. Testing may proceed without the patient information, however, the information aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send with the specimen.



Specimen Required


Specimen Type: Whole blood

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated


Forms

1. Rare Coagulation Disorder Patient Information (T824) is required.

2. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576

-Informed Consent for Genetic Testing (Spanish) (T826)

3. If not ordering electronically, complete, print, and send an Coagulation Test Request (T753) with the specimen.

Useful For

Evaluating hereditary angioedema (HAE) with normal C1 inhibitor (C1INH) in patients with a suggestive personal or family history

 

Confirming a diagnosis of HAE with normal C1INH with the identification of a known or suspected disease-causing alteration in the F12, PLG or KNG1 gene

 

Determining the disease-causing alteration within the F12, PLG or KNG1 gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of HAE with normal C1INH

 

Evaluating factor XII deficiency in patients with a suggestive personal or family history

 

Confirming a factor XII deficiency diagnosis with the identification of known or suspected disease-causing alteration(s) in the F12 gene

 

Determining the disease-causing alteration(s) within the F12 gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of factor XII deficiency

 

Identifying the causative alteration(s) for genetic counseling purposes

 

Prognosis and risk assessment based on the genotype-phenotype correlations

 

Carrier testing for close family members of an individual with a diagnosis of factor XII deficiency

 

This test is not intended for prenatal diagnosis.

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

Hereditary Angioedema Panel, NGS

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Hereditary angioedema with normal C1 inhibitor (HAE with normal C1INH) is a rare blood and immunologic disorder associated with germline variants in the F12 gene (F12-HAE), PLG gene (PLG-HAE), and KNG1 gene (KNG1-HAE). It is inherited in an autosomal dominant manner with incomplete penetrance.(3,4)

 

HAE with normal C1INH is characterized by recurrent episodes of severe skin and submucosal swelling, abdominal pain attacks, and upper airway obstruction that does not respond to high-dose antihistamine therapy. Facial and tongue swelling are common. Affected individuals have normal complement studies, normal C1INH antigen and function, and no exposure to medications that could cause angioedema, such as angiotensin-converting-enzyme inhibitors or non-steroidal anti-inflammatory drugs. Estrogen exposure exacerbates disease severity in many patients.(2-6)

 

Acquired angioedema is associated with B-cell lymphoproliferative disorders in some patients, the presence of autoantibodies to C1-INH, and the use of renin-angiotensin-aldosterone system-blockers.(4)

 

In addition to HAE with normal C1INH, germline variants in the F12 gene are associated with autosomal recessive factor XII deficiency. While this rare blood disorder is characterized by prolonged activated partial thromboplastin time and reduced factor XII activity, it is rarely associated with an excessive bleeding tendency or abnormal bleeding during trauma or surgery. Individuals with factor XII deficiency are generally asymptomatic.(7)

 

Causes of acquired (nongenetic) factor XII deficiency should be excluded prior to genetic testing, including liver disease, nephrotic syndrome, and chronic granulocytic leukemia.

Reference Values

An interpretive report will be provided.

Day(s) Performed

Varies

Report Available

28 to 42 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81479