A novel mutation in intron K of the PROS1 gene causes aberrant RNA splicing and is a common cause of protein S deficiency in a UK thrombophilia cohort.
A hitherto unknown splice site defect in the protein S gene (PROS1): the mutation results in allelic exclusion and causes type I and type III protein S deficiency.
We have used a strategy of specific amplification of the coding regions and intron/exon boundaries of the active protein S gene (PROS1) and direct single-strand solid phase sequencing, to seek mutations in 35 individuals with phenotypic protein S deficiency.
Sixteen Danish unrelated thrombophilic families with plasma protein S deficiency of type 1 (or III) are currently under investigation in our laboratory for defects in the protein S alpha gene.
Antenatal diagnosis in a second pregnancy was initially performed by indirect restriction fragment length polymorphism (RFLP) tracking using a neutral dimorphism within the PROS gene and served to exclude severe protein S deficiency.
These data agree with the notion that hereditary thrombophilia associated with protein S deficiency is indeed directly the result of a defect in the protein S gene.