Test Catalog

Molecular Diagnosis of Congenital Coagulopathies by NGS: Bernard-Soulier Syndrome

Code: 70814

Type: Estudi de coagulopaties congènites

Clinical information

Diagnostic Utility:

Identifying the molecular defect in the GP1BA, GP1BB, and GP9 genes in patients diagnosed with BSS.

Bernard-Soulier Syndrome (BSS)

BSS, also known as Bernard-Soulier syndrome or Hemorrhagiparous Thrombocytic Dystrophy, is a bleeding disorder associated with abnormal platelets. In affected individuals, platelets are unusually large and less numerous than normal (a combination known as macrothrombocytopenia). This syndrome is extremely rare, with only about 100 cases reported in the literature, although it is believed that this condition may be underdiagnosed. Clinical manifestations include epistaxis, menorrhagia, gingival bleeding, and gastrointestinal bleeding. Patients may experience severe and prolonged bleeding after minor injuries or surgery, or even spontaneously. In most cases, bleeding symptoms manifest rapidly after birth or during early childhood.

BSS is inherited in an autosomal recessive manner and is caused by mutations in the GP1BA, GP1BB, and GP9 genes. These genes encode three of the four subunits of the GPIb-V-IX receptor located on platelets. The main function of the GPIb-V-IX complex is to promote platelet adhesion to the sites of vascular injury by binding to von Willebrand factor (VWF), ensuring normal primary hemostasis.

Application of a multi-gene panel based on 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 the genes responsible for Bernard-Soulier syndrome (GP1BA, GP1BB, and GP9).

Method:

Next-generation sequencing of the exons and flanking intronic regions of GP1BA, GP1BB, and GP9 using a panel of genes related to congenital coagulopathies. These regions can also be analysed by traditional sequencing.

Traditional Sanger sequencing to confirm the detected mutation(s) in patients diagnosed with BSS, in order to obtain an unequivocal result by analysing the specific region where the variant is located.

If no potential or definitively causal mutation is identified, it will be reported and discussed with the requesting medical team the possibility of additional studies.

Reference Values

Not applicable

Diagnostic Algorithm:

Not applicable

Turnaround Time:

30 working days

Specimen information

Sample: Whole blood
Tub: 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 and/or incorrectly identified sample.

Other types of accepted samples:

  • Purified DNA, minimum of 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: Bernard-Soulier syndrome.
Synonyms: Genetic study of Bernard-Soulier syndrome, sequencing of GP1BA, GP1BB, and GP9.
Section: Congenital Coagulopathies
BST Rate: Check the updated rates here.

The checkbox B. SOULIER must be marked in the molecular study request form, 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