Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Prothrombin

Mutations that cause dysfuntion result in bleeding disorders, whereas a single genetic variation outside the coding region is associated with increased risk of thrombosis.

Epidemiology

The prevalence of this mutation is about 2,5%. In the South of Europe it is twice as high as in the North. In Africa und Asia this mutation is rather rare.

Gene Structure

The gene of Prothrombin or coagulation factor 2 (F2) is localized on chromosome 11 (11p11-q12). It is about 21kb in size and consists of 14 exons.

Phenotype

Patient with this mutation have a higher risk for thrombosis. These occur in atypical localizations for example in central ocular vein.

Pathology

There is a mutation in the prothrombin gene G20210A that causes hypercoagulability. It is not known yet what the mechanism is.

Gene Regulation

Prothrombin also called coagulation factor II cleaves in its active form (thrombin) fibrinogen and hereby forms fibrin the final product of the coagulation process. But thrombin is not only essential for coagulation it has a function in interrupting of the coagulation process.

Test Strategy

Patients with clinical evidence of thrombophilia. Family screening if a family member is a carrier.

Interpretation

The relative Risk for Thrombosis is 2-3.

Genetests:

Research Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Target mutation analysis
Turnaround 20 days
Specimen type genomic DNA

Related Diseases:

Thromboembolic diseases
Autosomal dominant protein C deficiency
PROC
Autosomal dominant protein S deficiency
PROS1
Autosomal recessive protein C deficiency
PROC
Autosomal recessive protein S deficiency
PROS1
F2
F5
Factor XII deficiency
F12
HABP2
Hyperhomocysteinemic thrombosis
CBS
Hypoplasminogenemia
Dysplasminogenemia
PLG
Hypoplasminogenemia
PLG
MTHFR
PAI transcription modulator
SERPINE1
Protein Z deficiency
PROZ
SERPINA10
SERPINC1
THBD
Thrombophilia due to heparin cofactor 2 deficiency
SERPIND1
VKORC1

References:

1.

Sun WY et al. (2001) Gene targeting in hemostasis. Prothrombin.

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2.

NCBI article

NCBI 2147 [^]
3.

OMIM.ORG article

Omim 176930 [^]
4.

Orphanet article

Orphanet ID 121671 [^]
5.

Wikipedia article

Wikipedia EN (Thrombin) [^]
Update: April 29, 2019