Summary
We describe molecular genetic studies of 15 patients with protein S deficiency type
I (i. e. reduced total protein S antigen). All the exons of the PROS 1 gene were analyzed
both by PCR and direct sequencing in all 15 probands. This analysis led to the identification
of point mutations affecting eight individuals. One of these mutations (codon -25,
insertion of T) has been described previously in a Dutch pedigree. The other mutations
are novel and all are located in exons that code for the protein S domain that is
homologous to the steroid hormone binding globulins. They include two amino acid replacements
(one individual with 340 Gly → Val, and two individuals with 467 → Val Gly), and four
frameshift mutations due to either one bp deletions (in codon 261 deletion of T and
in codon 267 deletion of G) or insertions (in codon 565 insertion T and after codon
578 insertion of C). Studies performed in six families (totalling 43 subjects) showed
cosegregation of the genetic abnormality with reduced plasma protein S levels, and
provided genetic evidence for a heterozygous protein S deficiency in 25 of them. The
yield of mutations in this study (53%) confirms that the percentage of protein S deficient
cases in which a point mutation is found remains low.
