Scientific background:

Summary: The gene encodes a crucial coagulation factor, which when deficient causes a serious bleeding disorder, but if the cleavage site is altered, then its inactivation is impossible, which results in untameable coagulation, an increased risk of thrombosis.

Gene: The gene F5 is about 70kb in size. It is located on Chromosome 1 (1q23). It consists of 25 exons.

Molecule: The structure is similar to coagulation factor VIII. We have the same domains (A1-A2-B-A3-C1-C2). The B domain is very much glycosilated.

Pathology: Mutations in this coagulation factor can cause either hemophilia or thrombophilia.

Clinical signs: The clinical picture depends on the type of mutation. If mutation results in thrombophilia we find thromboembolic diseases early in life. Characteristically the thrombosis might occur in atypical localizations. An influence on the development of cardiovascular disease is discussed too.

Epidemiology: The mutation factor V Leiden is of European origin. About 5% of the population in these countries is heterozygous. In Africa and Asia this mutation is rare. There are no broad statistical data concerning the other mutations of this gene.

Interpretation: The mutation factor V Leiden increases the annual risk for venous thrombosis up to 3 times in case of heterozygosity. In homozygous carriers the risk is about 28 times increased.

Test strategy: Patients suspected to have thrombophilia. Family screening.

Methodology:

	clinical test	Method		Hotspot sequencing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal and in some aspects external quality control
	Only in the region of interest, known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Fragment analysis
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Full external quality control
	Only the target mutation is detected all other genetic variations, though possibly important they may be, are missed.

Literature: 

Lee R et al. (2001) Factor V Leiden: a clinical review.