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

Parichat Pung-amritt; Swibertus R. Poort; Hans L. Vos; Rogier M. Bertina; Chularatana Mahasandana; Voravarn S. Tanphaichitr; Gavivann Veerakul; Suthida Kankirawatana; Vinai Suvatte

doi:10.1055/s-0037-1614440

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

¹From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

,

Swibertus R. Poort

²Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

,

Hans L. Vos

²Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

,

Rogier M. Bertina

²Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

,

Chularatana Mahasandana

¹From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

,

Voravarn S. Tanphaichitr

¹From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

,

Gavivann Veerakul

¹From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

,

Suthida Kankirawatana

¹From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

,

Vinai Suvatte

¹From the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

› Institutsangaben

Abstract

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.

Volltext

Referenzen

References
1 Davie EW, Fujikawa K, Kisiel W. The coagulation cascade: Initiation, maintenance and regulation. Biochemistry 1991; 30: 10363-70.
2 Engesser L, Broekmans AW, Briët E, Brommer EJP, Bertina RM. Hereditary protein S deficiency: Clinical manifestations. Ann Intern Med 1987; 106: 677-87.
3 Bertina RM. Prevalence of hereditary thrombophilia and identification of genetic risk factors. Fibrinolysis 1988; 2 (Suppl. 02) suppl. 7-13.
4 Allaart CF, Briët E. Familial venous thrombophilia. In: Haemostasis and Thrombosis. Bloom AL, Forbes CB, Thomas DP, Tuddenham EGD. (eds.) Edinburgh, Churchill Livingstone; 1994: pp 1349-60.
5 Mahasandana C, Suvatte V, Chuansumrit A, Marlar RA, Manco Johnson MJ, Jacobson LJ, Hathaway WE. Homozygous protein S deficiency in an infant with purpura fulminans. The Journal of Pediatrics 1990; 117 No (05) 750-3.
6 Pegelow CH, Ledford MR, Young J, Zilleruelo G. Severe protein S deficiency in a newborn. Pediatrics 1992; 89: 674-6.
7 Schmidel DK, Tatro AV, Tomazak JA, Long CL. Organization of the human protein S genes. Biochemistry 1990; 29: 7845-52.
8 Ploos van Amstel HK, Reitsma PH, van der Logt PE, Bertina RM. Intron-exon organization of the active human protein S gene PSα and its pseudogene PSβ: duplication and silencing during primate evolution. Biochemistry 1990; 29: 7853-61.
9 Edenbrandt CM, Lundwall A, Wydro R, Stenflo J. Molecular analysis of the gene for vitamin K-dependent protein S and its pseudogene. Cloning and partial gene organization. Biochemistry 1990; 29: 7861-8.
10 Ploos van Amstel JK, van der Zanden AL, Bakker E, Reitsma PH, Bertina RM. Two genes homologous with human protein S cDNA are located on chromosome 3. Thromb Haemost 1987; 58: 982-7.
11 Watkins P, Eddy R, Fukushima Y, Byers M, Cohen E, Dackowski W, Wydro R, Shows T. The gene for protein S maps near the centromere of human chromosome 3. Blood 1988; 71: 238-41.
12 Ploos van Amstel HK, Reitsma PH, Hamulyak K, de Die-Smulders CEM, Mannucci PM, Bertina RM. A mutation in the protein S pseudogene is linked to protein S deficiency in a thrombophilic family. Thromb Haemost 1989; 62: 897-901.
13 Dahlbäck B, Lundwall A, Stenflo J. Primary structure of bovine vitamin K-dependent protein S. Proc Natl Acad Sci USA 1986; 83: 4199-203.
14 Gandrille S, Borgel D, Ireland H, Lane DA, Simmonds R, Reitsma PH, Mannhalter C, Pabinger I, Saito H, Susuki K, Formstone C, Cooper DN, Espinosa Y, Sala N, Bernardi F, Aiach M. Protein S deficiency: A database of mutations. Thromb Haemost 1997; 77: 1201-14.
15 Mahansandana C, Veerakul G, Tanphaichitr VS, Suvatte V, Opartkiattikul N, Hathaway WE. Homozygous protein S deficiency: 7-year follow-up. Thromb Haemost 1996; 76: 1122.
16 Comp PC, Nixon RR, Cooper R, Esmon CT. Familial protein S deficiency is associated with recurrent thrombosis. J. Clin Invest 1984; 74: 2082-88.
17 Comp PC, Doray D, Patton D, Esmon CT. An abnormal plasma distribution of protein S occurs in functional protein S deficiency. Blood 1988; 67: 504-8.
18 Fair DS, Marlar RA. Biosynthesis and secretion of factor VII, protein C, protein S and the protein C inhibitor from a human hepatoma cell line. Blood 1986; 67: 64-70.
19 Marlar RA, EndreS-Brooks J, Miller C. Serial studies of protein C and its inhibitor in patients with disseminated intravascular coagulation. Blood 1985; 66: 59-63.
20 Koike Y, Sumi Y, Wakabayashi K, Ichikawa Y. The monoclonal antibody to human protein S that inhibits the binding of protein S to C4b-binding protein. Thromb Haemost 1989; 62 Abstract No 875.
21 Saiki RK, Schaaf S, Falvona F, Mullis KB, Horn GT, Ehrlich HA, Arnhiem N. Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985; 23: 1350-4.
22 Reitsma PH, Ploos van Amstel JK, Bertina RM. Three novel mutations in 5 unrelated subjects with hereditary protein S deficiency type I. J Clin Invest 1994; 93: 486-92.
23 Bertina RM, Ploos van Amstel JK, van Wijngaarden A, Coenen J, Leemhuis MP, Deutz-Terlouw PP, van der Linden IK, Reitsma PH. Heerlen polymorphism of protein S, an immunologic polymorphism due to dimorphism of residue 460. Blood 1990; 76: 538-48.
24 Sanger F, Nicklen S, Coulsen AR. DNA sequencing with chain terminating inhibitions. Proc Natl Acad Sci USA 1977; 74: 5463-7.
25 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
26 Chan WP, Lee CK, Kwong YL, Lam CK, Liang R. A novel mutation of Arg306 of factor V gene in Hong Kong Chinese. Blood 1998; 91: 1135-9.
27 Bertina RM. Rapid detection of the prothrombin 20210A variation by allele specific PCR. Thromb Haemost 1997; 78: 1157-63.
28 Bertina RM, Reitsma PH, Rosendaal FR, Vandenbroucke JP. Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis. Thromb Haemost 1995; 74: 449-53.
29 Rosendaal FR, Doggen CJM, Zivelin A, Arruda VR, Aiach M, Siscovick DS, Hillarp A, Watzke HH, Bernardi F, Cumming AM, Preston FE, Reitsma PH. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 1998; 79: 706-8.
30 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
31 Andersen BD, Lind B, Philips M, Hansen AB, Ingerslev J, Thorsen S. Two mutations in exon III of the protein S α gene in four thrombophilic families resulting in premature stop codons and depressed levels of mutated mRNA. Thromb Haemost 1996; 76: 143-50.
32 Cooper DN, Krawczak M. Mechanism of insertional mutagenesis in human genes causing genetic disease. Hum Genet 1991; 87: 409-15.
33 Raabe M. Letter to the editor: Long runs of adenines and human mutations. Amer J Med Genet 1998; 76: 101-2.
34 Cooper DN. Human gene mutations affecting RNA processing and translation. Ann Med 1993; 25: 11-7.
35 Nayler JA, Green PM, Rizza CR, Giannelli F. Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients. Hum Mol Genet 1993; 2: 11-17.
36 Koster T, Rosendaal FR, Briët E, van der Meer, Colly LP, Poort SR, Vandenbroucke JP. Protein C deficiency in a controlled series of unselected outpatients: An infrequent but clear risk factor for venous thrombosis. Leiden Thrombophilia Study (LETS). Blood 1995; 85: 2756-61.
37 Reitsma PH, Bernardi F, Doig RG, Gandrille S, Greengard JS, Ireland H, Krawczak M, Lind B, Long GL, Poort SR, Saito H, Sala N, Witt I, Cooper DN. Protein C deficiency: A database of mutations, 1995 update. Thromb Haemost 1995; 73: 876-89.
38 Tait RC, Walker ID, Reitsma PH, Islam SIAM, McCall F, Poort SR, Conkie JA, Bertina RM. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995; 73: 87-93.
39 Gomez E, Ledford MR, Pegelow CH, Reitsma PH, Bertina RM. Homozygous protein S deficiency due to a one base pair deletion that leads to a stop codon in exon III of the protein S gene. Thromb Haemost 1994; 71: 723-6.