General information
The SALSA MLPA
Probemix P112 PROS1 is a
research use only (RUO) assay for the detection of deletions or duplications in the
PROS1 gene, which is associated with hereditary protein S deficiency.
Protein S is a vitamin K-dependent glycoprotein that regulates blood coagulation (Ten Kate et al. 2008). It functions as a non-enzymatic cofactor for activated protein C (APC) in the proteolytic degradation of activated factor V and VIII, resulting in the inhibition of blood coagulation. Protein S circulates in plasma in two forms, a free form and a bound form in complex with C4b-binding protein (Ten Kate et al. 2008). Although both forms can act as cofactors, bound protein S is less effective than free protein S.
Hereditary protein S deficiency is an autosomal dominant disorder associated with an increased risk for venous thrombosis. In fact, while the prevalence of protein S deficiency is 0.2% in the general population, it is about 2% for patients with venous thrombosis (Ten Kate et al. 2008). There are three types of protein S deficiency that can be distinguished based on APC cofactor activity, total protein S and free protein S levels (Ten Kate et al. 2008). Type I is characterized by low levels of both total and free protein S and reduced APC cofactor activity. Type II shows normal levels of free and total protein S, but a reduced APC cofactor activity. Type III deficiency is characterized by normal total protein S levels and reduced free protein S
and APC cofactor activity. Large deletions/duplications within the
PROS1 locus have been identified as a relatively common cause of protein S deficiency (Pintao et al. 2009).
This SALSA MLPA probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.
Probemix content
The SALSA MLPA Probemix P112-A4 PROS1 contains 26 MLPA probes with amplification products between 136 and 382 nucleotides (nt). This includes 13 probes for the
PROS1 gene and one flanking probe for the
ARL13B gene located upstream of
PROS1. Furthermore, this probemix contains one probe for the protein S (beta) pseudogene (
PROSP or
PROS2 or
PROS2P), which shows 96.5% homology to exons 3 to 16 of the
PROS1 gene. In addition, 11 reference probes are included that detect autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes are available online (
www.mrcholland.com).
This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at
www.mrcholland.com.