Test Catalog

Molecular Diagnosis of Congenital Coagulopathies by NGS: Thrombotic Thrombocytopenic Purpura

Code: 70813

Type: Estudi de coagulopaties congènites

Clinical information

Diagnostic Utility:

Identifying the molecular defect in the ADAMTS13 gene in patients diagnosed with TTP.

Thrombotic Thrombocytopenic Purpura (TTP)

Congenital TTP, also known as Upshaw-Schulman Syndrome, is a very rare bleeding disorder, with only around 100 cases reported worldwide and an estimated annual incidence of less than 1/1,000,000. The congenital form of TTP is much less common than its acquired form (acquired TTP), accounting for 5% of all cases. Clinical manifestations vary widely, ranging from mild thrombocytopenia to severe hyperbilirubinemia with episodes of thrombocytopenia occurring shortly after childbirth. Patients may also develop neurological abnormalities, renal manifestations, cardiac dysfunction, and gastrointestinal symptoms due to generalized microvascular thrombosis.

This disease is inherited in an autosomal recessive manner and is caused by mutations in the ADAMTS13 gene. This gene encodes a metalloprotease that is involved in processing von Willebrand factor (VWF) by regulating the size of high-molecular-weight multimers. VWF interacts with platelets, facilitating their adhesion to the walls of blood vessels to form temporary blood clots. The enzyme ADAMTS13 cleaves the larger multimeric forms of VWF, preventing the formation of unnecessary blood clots.

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 the simultaneous molecular study of genes related to congenital coagulopathies and hereditary bleeding disorders, including the gene involved in Thrombotic Thrombocytopenic Purpura (ADAMTS13).

Method:

Next-generation sequencing of the exons and flanking intronic regions of ADAMTS13 with the application of a panel of genes related to congenital coagulopathies. These regions can also be analysed using traditional Sanger sequencing.

Traditional Sanger sequencing to verify the mutation(s) detected in patients diagnosed with TTP, 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 conducting 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 the refrigerator: 10 days

Transport instructions: Preferably at room temperature

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

Other accepted sample types:

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

Administrative information

BST Code: LRD2833
Test Description: Molecular diagnosis of congenital coagulopathies by NGS: Thrombotic Thrombocytopenic Purpura.
Synonyms: Genetic study of Thrombotic Thrombocytopenic Purpura, Molecular diagnosis of TTP, sequencing of ADAMTS13
Section: Congenital Coagulopathies
BST Rate: Check the updated rates here.

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

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