Test Catalog

Molecular diagnosis of congenital coagulopathies by NGS: Fibrinogen Deficiency

Code: 70810

Type: Estudi de coagulopaties congènites

Clinical information

Diagnostic Utility:

Identifying the molecular defect in the FGA, FGB or FGG genes in patients diagnosed with Fibrinogen Deficiency (DFG).

Fibrinogen Deficiency (DFG)

Congenital fibrinogen disorders are rare (1/1,000,000) and are classified as quantitative (afibrinogenemia, hypofibrinogenemia), functional (dysfibrinogenemia), or combined defects (hypodysfibrinogenemia). In afibrinogenemia, the most frequent clinical manifestations include umbilical cord bleeding, epistaxis, hemarthrosis, gastrointestinal bleeding, menorrhagia, traumatic and surgical bleeding, and rarely, intracranial hemorrhage. Additionally, women may experience prepartum, postpartum, and miscarriage bleeding. Patients diagnosed with hypofibrinogenemia present milder bleeding episodes after trauma or surgery. The majority of patients diagnosed with dysfibrinogenemia are asymptomatic (60%), although there are also cases with bleeding symptoms (28%) or thrombotic events (20%).

Congenital fibrinogen deficiencies are caused by mutations in the FGA, FGB, or FGG genes. Afibrinogenemia is transmitted in an autosomal recessive manner, while hypofibrinogenemia and dysfibrinogenemia have an autosomal dominant transmission. Recognizing the type of molecular defect is crucial for safer therapy, which will improve the clinical management of these patients.

Application of a multi-gene panel based on simultaneous amplification of exons and flanking intronic regions for sequencing through Next-Generation Sequencing (NGS) techniques allows for the simultaneous molecular study of genes related to congenital coagulopathies and hereditary bleeding disorders, including the fibrinogen genes (FGA, FGB, and FGG).

Method:

Next-Generation Sequencing of the exons and flanking intronic regions of FGA, FGB, and FGG using a gene panel related to congenital coagulopathies.

Traditional Sanger sequencing to confirm the detected mutation(s) by NGS in patients diagnosed with DFG, in order to reach an unequivocal result, analysing the specific region where the variant is located.

If no potential or definitively causative mutation is identified, it will be reported and discussed with the medical team requesting the test about the possibility of conducting complementary studies.

Reference Values

Not applicable

Diagnostic Algorithm:

Not applicable

Turnaround Time:

30 working days

Specimen information

Sample: Whole blood
Tube: EDTA K3 tube 5-10 ml if it is a blood sample
Minimum essential volume: 3 ml

Stability:

  • At room temperature: 4 days
  • In refrigeration: 10 days

Transport instructions: Preferably at room temperature

Reason for rejection: Coagulated and/or incorrectly identified sample.

Other types of accepted samples:

  • Purified DNA, minimum 300 ng (30 ng/μL)
  • Buccal mucosa: contact the laboratory to inquire about sample collection specifications.

Administrative information

BST Code: LDR2833
Test Description: Molecular diagnosis of congenital coagulopathies by NGS: Fibrinogen deficiency.
Synonyms: Genetic study of fibrinogen deficiency, sequencing of FGA, FGB and FGG.
Section: Congenital Coagulopathies
BST Rate: Check the updated rates here.

The box D. fibrinogen must be ticked on the molecular study request form and the available phenotypic data must be provided.

Profiles:

N/A.

References

  • Peter J Hulick. Next-generation DNA sequencing (NGS): Principles and clinical Applications. Waltham, MA: UpToDate Inc. https://www.uptodate.com
  • DNA Sequencing by Capillary Electrophoresis. Applied Biosystems Chemistry Guide. Second Edition.

Base de dades de mutacions