Thromb Haemost 1989; 62(03): 897-901
DOI: 10.1055/s-0038-1651024
Original Article
Schattauer GmbH Stuttgart

A Mutation in the Protein S Pseudogene Is Linked to Protein S Deficiency in a Thrombophilic Family

Hans K Ploos van Amstel
The Hemostasis and Thrombosis Research Unit, Department of Hematology, University Hospital, Leiden
,
Pieter H Reitsma
The Hemostasis and Thrombosis Research Unit, Department of Hematology, University Hospital, Leiden
,
Karly Hamulyák
1   Department of Biochemistry and Hematology, Faculty of Medicine, University of Limburg, Maastricht
,
Christine E M de Die-Smulders
2   Department of Clinical Genetics, University Hospital, Maastricht
,
Pier M Mannucci
3   A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milano, Italy
,
Rogier M Bertina
The Hemostasis and Thrombosis Research Unit, Department of Hematology, University Hospital, Leiden
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 07. Juni 1989

Accepted after revision 26. Juli 1989

Publikationsdatum:
24. Juli 2018 (online)

Summary

Probands from 15 unrelated families with hereditary protein S deficiency type I, that is having a plasma total protein S concentration fifty percent of normal, were screened for abnormalities in their protein S genes by Southern analysis. Two probands were found to have a deviating DNA pattern with the restriction enzyme Mspl. In the two patients the alteration concerned the disappearance of a Mspl restriction site, CCGG, giving rise to an additional hybridizing Mspl fragment.

Analysis of relatives of both probands showed that in one family the mutation does not co-segregate with the phenotype of reduced plasma protein S. In the family of the other proband, however, complete linkage between the mutated gene pattern and the reduced total protein S concentration was found: 12 heterozygous relatives showed the additional Mspl fragment but none of the investigated 26 normal members of the family. The mutation is shown to reside in the PSβ gene, the inactive protein S gene. The cause of type I protein S deficiency, a defect PSα gene has escaped detection by Southern analysis. No recombination has occurred between the PSα gene and the PSβ gene in 23 informative meioses. This suggests that the two protein S genes, located near the centromere of chromosome 3, are within 4 centiMorgan of each other.

 
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