Test Catalog

Molecular Diagnosis of Congenital Coagulopathies by NGS: Glanzmann Thrombasthenia

Code: LRD2833

Type: Estudi de coagulopaties congènites

Clinical information

Diagnostic Utility:

Identifying the molecular defect in the ITGA2B and ITGB3 genes in patients diagnosed with Glanzmann's thrombasthenia (GT).

Glanzmann's Thrombasthenia (GT)

GT is a rare bleeding disorder (prevalence unknown) characterized by a quantitative or qualitative deficiency of the protein called integrin alphaIIb/beta3 (αIIbβ3 or GPIIb/IIIa), located on the surface of platelets. Depending on the deficiency, three main categories are distinguished: type I with GPIIb/IIIa levels <5%; type II with levels 5-20%; and type III with a normal quantity of GPIIb/IIIa but with altered function. GT presents a wide clinical variability ranging from patients with only minimal bruising to others with frequent, severe, and potentially life-threatening bleeding. The most common bleeding symptoms in GT include epistaxis, gingival bleeding, and menorrhagia. On the other hand, gastrointestinal bleeding and hematuria are less common. In most cases, symptoms manifest rapidly after birth, although occasionally GT can be diagnosed at later stages.

This bleeding disorder is inherited in an autosomal recessive manner and is caused by mutations in the ITGA2B and ITGB3 genes. These genes encode two subunits of the integrin GPIIb/IIIa, promoting platelet aggregation to ensure the formation of a clot at sites of blood vessel injury.

Application of a multiple gene panel based on the simultaneous amplification of exons and flanking intronic regions for sequencing by next-generation sequencing (NGS) techniques allows for the simultaneous molecular study of genes related to congenital coagulopathies and hereditary bleeding disorders, including those involved in Glanzmann's Thrombasthenia (ITGA2B; ITGB3).

Method:

Next-generation sequencing of the exons and flanking intronic regions of ITGA2B and ITGB3 using a panel of genes related to congenital coagulopathies. These regions can also be analysed by traditional sequencing.

Traditional Sanger sequencing to confirm the mutation(s) detected in patients diagnosed with GT, 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, this will be reported and discussed with the requesting medical team to consider 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: Coagulated sample and/or incorrectly identified.

Other accepted sample types:

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

Administrative information

BST Code: LRD2833
Test Description: Molecular diagnosis of congenital coagulopathies by NGS: Glanzmann thrombasthenia.
Synonyms: Genetic study of Glanzmann thrombasthenia, sequencing of ITGA2B and ITGB3
Section: Congenital Coagulopathies
BST Rate: Check the updated rates here.

The checkbox T.Glanzmann must be ticked and the phenotypic data available must be completed on the molecular study request form.

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