Thromb Haemost 1999; 81(02): 189-192
DOI: 10.1055/s-0037-1614440
Review Articles
Schattauer GmbH

Compound Heterozygosity for One Novel and One Recurrent Mutation in a Thai Patient with Severe Protein S Deficiency

Parichat Pung-amritt
1   From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Swibertus R. Poort
2   Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
,
Hans L. Vos
2   Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
,
Rogier M. Bertina
2   Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
,
Chularatana Mahasandana
1   From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Voravarn S. Tanphaichitr
1   From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Gavivann Veerakul
1   From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Suthida Kankirawatana
1   From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Vinai Suvatte
1   From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
› Author Affiliations
We wish to thank Mrs. M.J. Mentink and Mrs. E.G. van Duijnen for skilful typing of the manuscript. We also express our thanks to the patient with her family and the normal Thai volunteers who participated in our study. The molecular studies were performed in the Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center (LUMC), The Netherlands. This work was supported by the Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Further Information

Publication History

Received09 July 1998

Accepted after revision22 September 1998

Publication Date:
08 December 2017 (online)

Summary

Homozygous or compound heterozygous protein S (PS) deficiency is a very rare disorder in the anticoagulant system, that can lead to life-threatening thrombotic complications shortly after birth. This report describes the results of the genetic analysis of the PROS1 genes in a Thai girl patient. She was reported in 1990 as the first case with homozygous PS deficiency and neonatal purpura fulminans. In the present report, we identified the mutations in this patient by direct sequencing of PCR products representing all 15 exons of the PROS1 gene and their flanking intronic regions. The patient turned out to be compound heterozygous for two null mutations. One allele contained a novel sequence variation, an A-insertion in an A5-tract covering codon 146 and 147, that results in a frameshift and a stop codon (TAA) at position 155. The other allele contained a nonsense mutation in exon 12 by a transition at codon 410 CGA (Arg) to TGA (stop). Cosegregation of PS deficiency with these two genetic defects was observed in her family.

 
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