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Thromb Haemost 2012; 108(01): 94-100
DOI: 10.1160/TH12-01-0040
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Small and large PROS1 deletions but no other types of rearrangements detected in patients with protein S deficiency

Christina Lind-Halldén
1   Kristianstad University, Section Biomedicine, Kristianstad, Sweden
,
Anna Dahlén
2   Section of Clinical Genetics, Lund University Hospital, Lund, Sweden
,
Andreas Hillarp
3   Department of Laboratory Medicine, Clinical Chemistry, Lund University, University Hospital Malmö, Malmö, Sweden
,
Bengt Zöller
4   Center for Primary Health Care Research, Malmö University Hospital, Malmö, Sweden
,
Björn Dahlbäck
3   Department of Laboratory Medicine, Clinical Chemistry, Lund University, University Hospital Malmö, Malmö, Sweden
,
Christer Halldén
1   Kristianstad University, Section Biomedicine, Kristianstad, Sweden
› Author Affiliations
Further Information

Publication History

Received: 23 January 2012

Accepted after major revision: 19 April 2012

Publication Date:
22 November 2017 (online)

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Summary

Protein S deficiency is a dominantly inherited disorder that results from mutations in the PROS1 gene. Previous sequencing of the gene failed to detect mutations in eight out of 18 investigated Swedish families, whereas segregation analyses detected large deletions in three out of the eight families. The present study investigates more thoroughly for the presence of deletions but also for other types of rearrangements. FISH analysis confirmed the existence of the three previously identified large deletions, but failed to identify any other type of rearrangement among the eight analysed families. MLPA analysis of the PROS1 gene revealed two smaller deletions covering two and four exons, respectively. Thus, deletions could be found in five out of eight families where no point mutations could be found despite sequencing of the gene. Twelve additional, not previously analysed, families were subsequently analysed using MLPA. The analysis identified two smaller deletions (3 and 4 exons). Including all PS-deficient families, i.e. also the 10 families where sequencing found a causative point mutation, deletions were identified in seven out of 30 PS-deficient families. A strategy of sequencing followed by MLPA analysis in mutation-negative families identified the causative mutation in 15 out of 18 of Swedish PS-deficient families. Most deletions were different as determined by their sizes, locations and flanking haplotypes. FISH (8 families) and MLPA analysis (20 families) failed to identify other types of rearrangements.

Keywords

Protein C/S pathway - molecular biology methods - familial thrombosis - venous thrombosis - thrombophilia

 

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