Analysis of the PROS1 gene by PCR amplification and sequencing of the coding region and splice junctions. Dosage analysis, via MLPA, is available as a second line test where gross deletions/ insertions are suspected.
Protein S is a co-factor for activated protein C and its deficiency leads to an increased risk of thrombophilia. Venous thrombosis occurs in 60-80% of patients heterozygous for protein S deficiency, generally before 40-45 years of age. It is an autosomal dominant disorder, caused by mutations in the PROS1 gene, with an estimated frequency of approximately 1 in 700. Homozygosity is very rare and results in life-threatening neonatal purpura fulminans.
Protein S deficiency is sub-classified as Type I (Quantitative), Type II (Qualitative) and Type III (low free PS / normal total PS). Mutations in PROS1 are less frequently identified in phenotypic Type III patients than in Type I and in some cases a lack of linkage to the PROS1 locus has been demonstrated.
Synonyms or keywords:
Protein S deficiency