Test Catalog

Diagnosis of congenital coagulopathies by NGS molecular: Factor II Deficiency

Code: LRD2833

Type: Estudi de coagulopaties congènites

Clinical information

Diagnostic Utility:

Identifying the molecular defect in F2 in patients diagnosed with IIHD.

Factor II Deficiency (IIHD)

IIHD, also known as prothrombin deficiency, is a bleeding disorder caused by a reduction in the activity of factor II (FII, prothrombin) and characterized by mucocutaneous bleeding manifestations. This deficiency has a prevalence of 1/2,000,000. It affects both sexes equally and can manifest at any age, although severe forms generally manifest early in life. Two main phenotypes are distinguished: hypoprothrombinemia with decreased activity and antigen level, and dysprothrombinemia with normal synthesis but a dysfunctional protein. The most common clinical manifestations include: epistaxis, menorrhagia, bleeding in the oral cavity, bleeding in the mucous membranes, bleeding in soft tissues, hemarthrosis, easy bruising, and prolonged bleeding after dental extraction, trauma, or surgery. The severity of bleeding manifestations is correlated with FII levels. 

IIHD has an autosomal recessive inheritance and is caused by mutations in the F2 gene (F2), which encodes prothrombin. More than 50 mutations have been detected that cause this deficiency. Some mutations drastically reduce prothrombin activity and can cause severe bleeding episodes. Other mutations allow moderate activity, which generally leads to mild bleeding episodes. However, none of the identified mutations completely eliminate prothrombin function.

Application of a multiple gene panel based on simultaneous amplification of exons and flanking intronic regions for sequencing using next-generation sequencing (NGS) techniques allows for the simultaneous molecular study of genes related to congenital coagulopathies and hereditary bleeding disorders, including the Factor II gene (F2).

Method:

Next-generation sequencing (NGS)

Massive sequencing of the exons and flanking intronic regions of F2 using a gene panel related to congenital coagulopathies.

Traditional Sanger sequencing to confirm the detected mutation(s) by NGS in patients diagnosed with IIHD, in order to reach an unequivocal result by 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 requesting medical team the possibility of performing additional studies.

Reference Values

Not applicable

Diagnostic Algorithm:

Not applicable

Turnaround Time:

20 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 the refrigerator: 10 days

Transport instructions: Preferably at room temperature

Reasons for rejection: Clotted sample and/or incorrectly identified.

Other types of accepted samples:

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

Administrative information

BST Code: LRD2833
Test Description: Molecular diagnosis of congenital coagulopathies by NGS: Factor II deficiency.
Synonyms: Genetic study of FII, molecular study of prothrombin, sequencing of F2.
Section: Congenital Coagulopathies
BST Rate: Check the updated rates here.

In the molecular study request form, the DFII box must be checked and the available phenotypic data filled in.

Profiles:

Not applicable.

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