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HelpTest Code GNFIB Congenital Fibrinogen Disorders, FGA, FGB, and FGG Genes, Next-Generation Sequencing, Varies
Ordering Guidance
This test is designed to detect single nucleotide and copy number variants in the FGA, FGB, and FGG genes associated with congenital fibrinogen disorders (CFD).
This test should only be considered if coagulation screening tests measuring thrombin clotting time (TT; with or without reptilase time), clottable fibrinogen, and fibrinogen antigen suggest a quantitative or functional defect in fibrinogen, especially if these findings are similar between family members.
For assessment of thrombin clotting time, order TTSC / Thrombin Time (Bovine), Plasma.
For assessment of fibrinogen function, order FIBTP / Fibrinogen, Plasma.
For assessment of fibrinogen quantity, order FIBAG / Fibrinogen Antigen, Plasma.
If genetic testing for CFD using a larger panel is desired, both a 25-gene comprehensive bleeding panel and a 16-gene comprehensive thrombosis panel are available. See GNBLC / Bleeding Disorders, Comprehensive Gene Panel, Next-Generation Sequencing, Varies; and GNTHR / Thrombosis Disorders, Comprehensive Gene Panel, Next-Generation Sequencing, Varies.
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.
Additional Testing Requirements
All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen as this must be a different order number than the prenatal specimen.
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
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
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
Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20 mL
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional information:
1. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid.
2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Chorionic villi
Container/Tube: 15-mL tube containing 15 mL of transport media
Specimen Volume: 20 mg
Specimen Stability Information: Refrigerated
Additional Information:
1. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing.
2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Acceptable:
Specimen Type: Confluent cultured cells
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured cells from another laboratory.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
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.
Secondary ID
619159Useful For
Evaluating congenital fibrinogen disorders (CFD) in patients with a personal or family history suggestive of a fibrinogen disorder
Confirming a CFD diagnosis with the identification of known or suspected disease-causing alterations in the FGA, FGB, or FGG genes
Determining the disease-causing alterations within the FGA, FGB, or FGG genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of suggestive of CFD
Identifying the causative alterations for genetic counseling purposes
Prognosis and risk assessment based on the genotype-phenotype correlations
Carrier testing for close family members of an individual with autosomal recessive afibrinogenemia/hypofibrinogenemia
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
| CULAF | Amniotic Fluid Culture/Genetic Test | Yes | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
The clinical workup congenital fibrinogen disorders (CFD) should begin with global coagulation screening assays.
In afibrinogenemia, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin clotting time (TT) may be infinitely prolonged.
In hypofibrinogenemia, TT is more sensitive than PT or aPTT for both quantitative and qualitative defects in fibrinogen. Reptilase time (RT) may be performed in addition to, or instead of, TT in specimens known, or suspected, to contain heparin, which artificially prolongs TT.
Further screening and identification of a mild fibrinogen deficiency or dysfibrinogenemia require a clottable fibrinogen assay (typically Clauss-method based) to assess fibrinogen function and an immunologic (antigenic) assay to assess fibrinogen quantity. Hypofibrinogenemia is indicated by a proportional reduction of both antigen and functional plasma fibrinogen concentrations. Dysfibrinogenemia is indicated by the combined presence of normal antigen amounts and reduced functional levels of circulating fibrinogen.(1-3)
Genetic testing for CFD is indicated if:
-Coagulation tests indicate a quantitative or functional defect in fibrinogen
-Acquired causes of fibrinogen disorders have been excluded (eg, liver disease, disseminated intravascular coagulopathy, trauma-induced coagulopathy, medications such as L-asparaginase, multiple myeloma or other malignancy, the use of plasma exchange using albumin as a replacement fluid, rheumatoid arthritis, systemic lupus erythematosus)
For prenatal specimens only:
-If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added at an additional charge.
-If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added at an additional charge.
For any prenatal specimen that is received, maternal cell contamination testing will be performed at an additional charge.
Special Instructions
Method Name
Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reporting Name
FGA/B/G Genes, Full Gene NGSSpecimen Type
VariesSpecimen Minimum Volume
Blood: 1 mL; Amniotic fluid: 10 mL; Other specimen types: see Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Reject Due To
All specimens will be evaluated by Mayo Clinic Laboratories for test suitability.Clinical Information
Congenital fibrinogen disorders (CFD) are rare bleeding abnormalities associated with germline variants in the FGA, FGB, and FGG genes. They manifest as one of 2 broad subtypes: autosomal recessive afibrinogenemia/hypofibrinogenemia (also known as a type I fibrinogen defect) or autosomal dominant dysfibrinogenemia (also known as a type II defect).
Afibrinogenemia and hypofibrinogenemia are considered quantitative defects characterized by undetectable or low levels of fibrinogen, respectively. Afibrinogenemia often presents in the neonatal period as umbilical cord bleeding. However, a later age of onset is not unusual and bleeding in the skin, oral cavity, gastrointestinal tract, genitourinary tract, and the central nervous system can occur. Individuals with hypofibrinogenemia are typically asymptomatic due to fibrinogen levels that, while lower than normal, are adequate to protect against spontaneous bleeding.
Dysfibrinogenemia is considered a qualitative defect. It is caused by structural changes in fibrinogen that modify its function, resulting in impaired clotting ability. Individuals with dysfibrinogenemia are commonly asymptomatic or have episodic symptoms. Cases are frequently discovered incidentally during routine coagulation testing or because of a positive family history.
Patients with CFD can also present with thrombotic events. Affected women are at increased risk of obstetric complications, including pregnancy loss, placental abruption, and postpartum hemorrhage.(3-6)
Causes of acquired (nongenetic) fibrinogen disorders should be excluded prior to genetic testing, including liver disease, consumptive coagulopathy (eg, disseminated intravascular coagulopathy, trauma-induced coagulopathy, medications (eg, L-asparaginase), malignancy (eg, multiple myeloma), the use of plasma exchange using albumin as a replacement fluid, and autoimmune conditions resulting in antifibrinogen antibodies (e.g., rheumatoid arthritis and systemic lupus erythematosus).(3,4)
The United Kingdom Haemophilia Centre Doctors' Organization provides guidelines regarding diagnosis and management for individuals with inherited bleeding disorders including fibrinogen deficiency.(7)
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(8) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Method Description
Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the FGA, FGB, and FGG genes, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp, and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the FGA, FGB, and FGG genes.
There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Congenital Fibrinogen Disorders, FGA, FGB, and FGG Genes and Methodology Details for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)
The reference transcript for FGA is NM_000508.5, FGB is NM_005141.4, and FGG is NM_000509.5 and NM_021870.3. Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing. Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.
Day(s) Performed
Varies
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
88233-Tissue culture, skin, solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
88235-Amniotic fluid culture (if appropriate)
81265-Maternal cell contamination (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| GNFIB | FGA/B/G Genes, Full Gene NGS | 92992-7 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 619160 | Test Description | 62364-5 |
| 619161 | Specimen | 31208-2 |
| 619162 | Source | 31208-2 |
| 619163 | Result Summary | 50397-9 |
| 619164 | Result | 82939-0 |
| 619165 | Interpretation | 59465-5 |
| 619166 | Additional Results | 82939-0 |
| 619167 | Resources | 99622-3 |
| 619168 | Additional Information | 48767-8 |
| 619169 | Method | 85069-3 |
| 619170 | Genes Analyzed | 82939-0 |
| 619171 | Disclaimer | 62364-5 |
| 619172 | Released By | 18771-6 |