Large deletions of the PROS1 gene in a large fraction of mutation-negative patients with protein S deficiency

Anna M. Johansson; Andreas Hillarp; Torbjörn Säll; Bengt Zöller; Björn Dahlbäck; Christer Halldén

doi:10.1160/TH05-06-0392

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(05): 951-957
DOI: 10.1160/TH05-06-0392

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Large deletions of the PROS1 gene in a large fraction of mutation-negative patients with protein S deficiency

Anna M. Johansson

¹Department of Cell and Organism Biology, Lund University, Lund, Sweden

,

Andreas Hillarp

¹Department of Cell and Organism Biology, Lund University, Lund, Sweden

,

Torbjörn Säll

¹Department of Cell and Organism Biology, Lund University, Lund, Sweden

,

Bengt Zöller

¹Department of Cell and Organism Biology, Lund University, Lund, Sweden

,

Björn Dahlbäck

¹Department of Cell and Organism Biology, Lund University, Lund, Sweden

,

Christer Halldén

²Department of Clinical Chemistry, University Hospital, Malmö, Sweden

› Author Affiliations

Abstract

Summary

Protein S deficiency is an autosomal dominant disorder that results from mutations in the PROS1 gene. Conventional mutation detection techniques fail to detect a pathogenic PROS1 mutation in approximately 50% of cases. The present study investigates whether large deletions of PROS1 are found in families where mutations in the PROS1 gene have not been found despite sequencing. For this purpose, a dense set of SNP and microsatellite markers were used in segregation analysis to identify deletions. Large deletions were identified by this technique in three out of eight investigated families (38%). The deletions encompassed at least 35 kb, 437 kb and 449 kb respectively. The deletions were confirmed by quantitative PCR. Haplotype analysis showed that the three large deletions and the five other disease haplotypes were all different. All of the eight disease haplotypes co-segregated with protein S deficiency, but each of the five non-deletion haplotypes were present also in normal individuals. In conclusion: Large deletions of PROS1 are relatively common in protein S deficiency patients and screening for large deletions in PROS1 mutation-negative individuals are therefore warranted.

Keywords

Deletion - mutation - protein S deficiency - PROS1

Full Text

References

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