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Thromb Haemost 1995; 73(05): 750-755
DOI: 10.1055/s-0038-1653863
Original Articles
Clinical Studies
Schattauer GmbH Stuttgart

Identification of Eight Point Mutations in Protein S Deficiency Type I – Analysis of 15 Pedigrees

P H Reitsma
The Thrombosis and Hemostasis Research Center, Department of Hematology, University Hospital, Leiden, The Netherlands
,
E Gómez
The Thrombosis and Hemostasis Research Center, Department of Hematology, University Hospital, Leiden, The Netherlands
,
S R Poort
The Thrombosis and Hemostasis Research Center, Department of Hematology, University Hospital, Leiden, The Netherlands
,
R M Bertina
The Thrombosis and Hemostasis Research Center, Department of Hematology, University Hospital, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 30 December 1994

Accepted after revision 15 February 1995

Publication Date:
09 July 2018 (online)

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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.

 

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