Familial Hypofibrinogenaemia and Dysfibrinogenaemia: FGA, FGB, FGG Sequencing

Diagnostic Use

Classical dysfibrinogenaemias results from an impairment of fibrin polymerisation. They are associated with prolonged thrombin clotting times and low functional, but normal antigenic fibrinogen concentrations, and are usually caused by point mutations in the regions of the fibrinogen chain genes coding for functional domains involved in polymerisation.

Hypofibrinogenaemias are associated with low functional and antigenic concentrations (less than 1.5 mg/mL) and can result from a variety of different mutations. These can affect either transcription, mRNA processing, translation, polypeptide chain processing and assembly, export from the hepatocyte, or the stability of the mature protein. Although heterozygosity for any such mutations might reduce fibrinogen levels below the normal range, they would not usually be expected to produce a significant clinical condition unless inherited in a homozygous, or compound heterozygous state. In this case afibrinogenaemia may result, and lead to a serious bleeding condition.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

dysfibrinogenaemia
FGA, FGB, FGG gene analysis
Fibrinogen gene analysis
hypofibrinogenaemia

Turnaround Time

4 weeks

Test Code

4575

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Pre-testing Requirements

Coagulation investigation (TCT, Clauss fibrinogen).

Additional Specimen Information

This test requires nucleated cells. Please do not centrifuge or freeze blood samples
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

This test requires nucleated cells. Please do not centrifuge or freeze blood samples
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Test Method

For suspected dysfibrinogenaemia or hypofibrinogenaemia, initial analysis is by time-of-flight mass spectrometry (TOF-MS) which usually identifies whether the fibrinogen A-alpha (FGA), B-beta (FGB), or gamma (FGG) chains have a mutation. DNA sequencing of FGA/FGB/FGG genes is then performed to identify and/or confirm a mutation.

Contact Canterbury Health Laboratories on +64 3 364 0484 or email LabInfo@cdhb.health.nz

Additional Costing Information

The cost for testing depends on the amount of analysis required; TOF-MS analysis plus DNA sequencing of a single exon is approximately $475; if full sequencing of FGA, FGB, and FGG genes is required the cost is approximately $1000.

Uncertainty of Measurement Automated bidirectional DNA sequencing has an analytical sensitivity and specificity of >99%. Note that the lower limit of variant detection of sequencing analysis is ~10%, this is important to consider in the case of mosaicism, mitochondrial, and somatic variation that is not expected to be present at 50% or 100%. This analysis will not detect variants located within intronic regions, except at the intron-exon boundaries.

Genomic DNA must be extracted from the specimen prior to testing. This incurs an additional charge (see GDNA). Laboratories may prefer to submit DNA for testing. Please provide a minimum of 5 micrograms of DNA at 20 nanograms/microlitre.

Contact Information

Enquiry Form