Factor V Leiden
| Factor V Leiden thrombophilia | |
|---|---|
| Classification and external resources | |
| Specialty | Hematology |
| ICD-10 | D68.5 |
| ICD-9-CM | 289.81 |
| OMIM | 188055 |
| DiseasesDB | 154 |
| SNP: Factor V Leiden | |
|---|---|
| Name(s) | Factor V Leiden, Arg506Gln, R506Q, G1691A |
| Gene | Factor V |
| Chromosome | 1 |
| External databases | |
| Ensembl | Human SNPView |
| dbSNP | 6025 |
| HapMap | 6025 |
| SNPedia | 6025 |
| HgenetInfoDB | 6025 |
| ALFRED | SI001216K |
Factor V Leiden thrombophilia is a genetic disorder of blood clotting. Factor V Leiden is a variant (mutated form) of human factor V (one of several substances that helps blood clot) that causes an increase in blood clotting (hypercoagulability). With this mutation, the anticoagulant protein secreted (that stops factor V from causing inappropriate clotting) is inhibited, leading to an increased tendency to form dangerous, abnormal blood clots. Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorder amongst ethnic Europeans. It is named after the Dutch city Leiden, where it was first identified in 1994 by Prof R. Bertina et al.
Abnormal, recurrent venous thromboses.
In the normal person, factor V functions as a cofactor to allow factor Xa to activate prothrombin, resulting in the enzyme thrombin. Thrombin in turn cleaves fibrinogen to form fibrin, which polymerizes to form the dense meshwork that makes up the majority of a clot. Activated protein C (aPC) is a natural anticoagulant that acts to limit the extent of clotting by cleaving and degrading factor V.
Factor V Leiden is an autosomal dominant genetic condition that exhibits incomplete penetrance, i.e. not every person who has the mutation develops the disease. The condition results in a factor V variant that cannot be as easily degraded by aPC (activated Protein C). The gene that codes the protein is referred to as F5. Mutation of this gene—a single nucleotide polymorphism (SNP) is located in exon 10. As a missense substitution of base G to base A, it changes the protein's amino acid from arginine to glutamine. Depending on the chosen start the position of the nucleotide variant is either at position 1691 or 1746. It also affects the amino acid position for the variant, which is either 506 or 534. (Together with the general lack of nomenclature standard, this variance means that the SNP can be referred to in several ways, such as G1691A, c.1691G>A, 1691G>A, c.1746G>A, p.Arg534Gln, Arg506Gln, R506Q or rs6025.) Since this amino acid is normally the cleavage site for aPC, the mutation prevents efficient inactivation of factor V. When factor V remains active, it facilitates overproduction of thrombin leading to generation of excess fibrin and excess clotting.
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