Test Catalog

Molecular diagnosis of congenital coagulopathies by NGS: Combined Deficiency of Factor V and Factor XIII

Code: 70802

Type: Estudi de coagulopaties congènites

Clinical information

Diagnostic Utility:

Identifying the molecular defect in the LMAN1 and MCFD2 genes in patients diagnosed with DFVWFVIII.

Combined Deficiency of Factors V and VIII (DFVWFVIII)

DFVWFVIII is a disorder caused by decreased levels of activity and antigen of both factor V (FV) and factor VIII (FVIII), characterized by mild to moderate hemorrhagic symptoms. The prevalence is estimated between 1/100,000 and 1/1,000,000. This condition is more common in the Mediterranean area and in areas where consanguineous marriages are common. The most common symptoms include epistaxis, easy bruising, post-operative or post-partum hemorrhage, and menorrhagia. Hemarthrosis and muscle hematomas can occur. Symptoms are usually mild. Levels of factors V and VIII range between 1-46% and present manifestations of mild to moderate bleeding, with onset at any age.

DFVWFVIII has an autosomal recessive inheritance pattern and is caused by mutations in the MCFD2 and LMAN1 genes, which encode proteins involved in the intracellular transport of FV and FVIII. 70% of mutations affect LMAN1, while the remaining 30% affect MCFD2.

Application of a multi-gene panel based on simultaneous amplification of exons and flanking intronic regions for sequencing using next-generation sequencing (NGS) techniques allows for simultaneous molecular study of genes related to congenital coagulopathies and hereditary bleeding disorders, including the Combined Deficiency of FV and FVIII genes (MCFD2; LMAN1).

Method:

Next-generation sequencing of the exons and flanking intronic regions of LMAN1 and MCFD2 using a panel of genes related to congenital coagulopathies.

Sanger traditional sequencing to confirm the mutation(s) detected by NGS in patients diagnosed with DFVWFVIII, in order to obtain an unequivocal result by analyzing 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 about the possibility of additional 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: 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 specimen collection specifications.

Administrative information

BST Code: LRD2833
Test Description: Molecular diagnosis of congenital coagulopathies by NGS: Combined Deficiency of Factor V and VIII.
Synonyms: Genetic study of DFVFVIII, sequencing of LMAN1 and MCFD2.
Section: Congenital Coagulopathies
BST Rate: Check the updated rates here.

On the molecular study request form, the DFV+DFVIII box must be checked and the available phenotypic data must be filled in.

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