Scientific background:

Summary: This protein plays an important role in taming blood coagulation, so inactivating mutations bring about a higher risk of intravascular coagulation, increased risk of thrombosis.

Gene: The gene is abreviated PROC. Its locus is on chromosom 2 (2q13-q14). Size is about 11kb. I consists of 9 exons but only 8 of them are translated.

Pathology: The protein product is a vitamin K dependent proteinase. When activated this enzyme (APC) inactivates the active coagulation factors Va and VIIIa and in the same time it increases fibrinolytic activity. Cofactor for these processes is protein S.

Clinical signs: Homozygous carrier of this mutation are extremely rare. They can be found when a newborn child suffers from some thromboembolic diseases. Heterozygous carriers develop venous Thrombosis. This occurs in 80% before age of 40. Most often the first such event occurs during pregnancy. Necrosi due to therapy with oral anticoagulants are most often in protein C deficiency. Sekundary protein C deficiencies have to be excluded.

Epidemiology: The prevalence of protein C deficiency is 0,2-0,4%. This portion is higher, when patients with venous thrombosis are preselected an goes up to 2 to 13%.

Interpretation: The risk of venous thrombosis is elevated for about 7,3 in carriers of protein C mutations.

Test strategy: Patient with biochemical evidence of Protein C deficiency when a secondary reason is excluded. Family screening if a family member is a carrier.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		medium
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Multiplex Ligation-Dependent Probe Amplification
		Turn-around time		25 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

Kraus M et al. (1998) The anticoagulant potential of the protein C system in hereditary and acquired thrombophilia: pathomechanisms and new tools for assessing its clinical relevance.
Foster DC et al. (1985) The nucleotide sequence of the gene for human protein C.