Test Catalog

Molecular Diagnosis of Congenital Coagulopathies by NGS: Factor XI Deficiency

Code: LRD2833

Type: Estudi de coagulopaties congènites

Clinical information

Diagnostic Utility:

Identifying the molecular defect in F11 in patients diagnosed with DFXI.

Factor XI Deficiency (DFXI)

DFXI is a bleeding disorder caused by a reduction in levels and/or activity of factor XI (FXI) that leads to moderate bleeding symptoms, usually after trauma or surgery. The estimated prevalence is approximately 1/1,000,000. However, severe DFXI is much more common in individuals with Ashkenazi Jewish ancestry from Central and Eastern Europe, affecting approximately 1 in 450 individuals in this population due to high consanguinity. The disease affects both men and women equally and can manifest at any age. Bleeding occurs after circumcision, dental extractions, trauma, or surgery. Generally, patients do not experience spontaneous bleeding, but women may have menorrhagia. The bleeding is usually moderate. Undiagnosed and untreated patients may develop significant hematomas after a surgical procedure. Unlike most coagulation factor deficiencies, the severity of bleeding manifestations is poorly correlated with FXI levels.

DFXI is caused by mutations in F11, which controls the production of plasma FXI. The transmission is mainly autosomal recessive, but cases of heterozygous patients with bleeding symptoms have also been observed, suggesting the possibility of autosomal dominant transmission.

Application of a multiple 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 Factor XI gene (F11).

Method:

Next Generation Sequencing (NGS)

NGS of the exons and flanking intronic regions of F11.

Traditional Sanger sequencing to confirm the mutation(s) detected by NGS in patients diagnosed with DFXI, in order to reach an unambiguous 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 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's a blood sample
Minimum necessary volume: 3 ml

Stability:

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

Transport instructions: Preferably at room temperature

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

Other accepted sample types:

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

Administrative information

BST Code: LRD2833
Test Description: Molecular diagnosis of congenital coagulopathies by NGS: Factor XI Deficiency.
Synonyms: Genetic study of DFXI, sequencing of F11.
Section: Congenital Coagulopathies
BST Rate: Check the updated rates here.

The molecular study request form must be checked the DFXI box and fill in the available phenotypic data.

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