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DOI: 10.1055/s-0038-1642512
Homzygous Protein S Deficiency due to a One Base Pair Deletion that Leads to a Stop Codon in Exon III of the Protein S Gene
Publication History
Received: 08 December 1993
Accepted after revision: 24 February 1994
Publication Date:
09 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199406/lookinside/thumbnails/10-1055-s-0038-1642512-1.jpg)
Summary
Homozygous protein S (PS) deficiency is a very rare disorder that causes purpura fulminans in affected newborns. This report describes the molecular genetic abnormality of a severe PS deficient child who developed purpura fulminans shortly after birth. The mutation was identified as a deletion of one adenine in codon 43 of exon III of the PROS 1 gene. This mutation results in a frameshift and a novel stop codon at position 45. The proband was apparently homozygous and his mother heterozygous for this mutation. The proband’s father was not available for study.
The single base pair deletion predicts a truncated translation product, where Lys 43 and Tyr 44 have been replaced by Asn 43 and Thr 44. This putative protein (predicted mw of 5.696 daltons) contains only the gammacarboxyglutamic acid (Gla) domain and the aromatic stack.
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References
- 1 Suzuki K, Nishioka J, Hashimoto R. Regulation of activated protein C by thrombin-modified protein S. J. Biochem 1983; 94: 699-705
- 2 Fulcher CA, Gardiner JE, Griffin JH, Zimmerman TS. Proteolytic inactivation of human factor VIII procoagulant protein by activated human protein C and its analogy with factor V. Blood 1984; 63: 486-9
- 3 Walker FJ. Regulation of activated protein C by protein S. J Biol Chem 1981; 256: 11128-32
- 4 Heeb MJ, Rosing HM, Fernández TA, Tans G, Griffin JH. Plasma protein S binds to and inhibits factor Xa. Blood 1992; 80: 1-1040 (Abstr. 1040).
- 5 Dahlbäck B, Stenflo J. High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein. Proc Natl Acad Sci USA 1981; 78: 2512-6
- 6 Comp PC, Nixon RR, Cooper MR, Esmon CT. Familial protein S deficiency is associated with recurrent thrombosis. J Clin Invest 1984; 74: 2082-8
- 7 Schwarz HP, Fischer M, Hopmeier P, Batard MA, Griffin JH. Plasma proteinS deficiency in familial thrombotic disease. Blood 1984; 64: 1297-1300
- 8 Droekmans AW, Bertina RM, Reinalda-Pool J, Engesser L, Muller HP, Leeuw JA, Michiels JJ, Brommer FI P, Briët F. Hereditary proteinS deficiency and venous thrombo ebmohsm. A study in three Dutch families. Thromb Haemost 1985; 53: 273-7
- 9 Bertina RM. Hereditary proteinS deficiency. Haemostasis 1985; 15: 241-4
- 10 Engesser L, Broekmans AW, Briët E, Brommer EJ P, Bertina RM. Hereditary protein S deficiency: clinical manifestations. Ann Intern Med 1987; 106: 677-82
- 11 Allaart CF, Aronson DC, Ruys T. et al. Hereditary protein S deficiency in young adults with arterial occlusive disease. Thromb Haemost 1990; 64: 206-10
- 12 Girolani A, Simioni P, Lazzaro AR. et al. Heterozygous protein S deficiency: A study of a large kindred. Acta Haematol 1990; 84: 162-8
- 13 Briët E, Broekmans AW, Engesser L. Hereditary protein S eficiency. In: Protein C and related proteins. Bertina (ed). Churchill Livingstone, Edinburgh; 1988: 203-32
- 14 Bertina R. Prevalence of hereditary thrombophilia and the identification of genetic risk factors. Fibrinolysis 1988; 2 (s2): 7-13
- 15 Chafa O, Fischer AM, Menane F, Chellali F, Rahal S, Sternberg C, Bernabadji M. A new case of “type II” inherited protein S deficiency. Br J Haematol 1989; 73: 501-5
- 16 Mahasandana C, Suvatte V, Marlar RA, Manco-Johnson MJ, Jacobson LJ, Hathaways WE. Neonatal purpura fulminans associated with homozygous protein S deficiency. Lancet 1990; 335: 61-2
- 17 Pegelow CH, Ledford M, Young J, Zilleruelo G. Severe protein S deficiency in a newborn. Pediatrics 1992; 89: 674-6
- 18 Watkins PC, Eddy R, Fu Kushima Y, Ryers MG, Cohen EH, Dackowski WR, Wydro RM, Shows TB. The gene for protein S maps near the centromere of human chromosome 3. Blood 1988; 71: 238-41
- 19 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; 8: 982-7
- 20 Ploos van Amstel HK, Reitsma PH, van der Logt CP E, Bertina RM. Intron-exon organization of the active human protein S gene PSa and pseudogene PS(3: duplication and silencing during primate evolution. Biochemistry 1990; 29: 7853-61
- 21 Schmidel DK, Tatso AV, Phelps LG, Tomczak JA, Long GL. Organization of the human protein S genes. Biochemistry 1990; 29: 7845-52
- 22 Edenbrandt CM, Lindwall 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
- 23 Deutz-Terlouw PP, Ballering L, van Wijngaarden A, Bertina RM. Two ELISA’s for measurement of protein S. and their use in the laboratory diagnosis of protein S deficiency. Clinica Chimica Acta 1989; 186: 321-34
- 24 Bertina RM, Ploos van Amstel HK, van Wijngaarden A, Coenen J, Leemhuis MP, Deutz-Terlouw RP, van der Linden IK, Reitsam PH. Heerlen polymorphism of protein S. an immunologic polymorphism due to dimorphism of residue 460. Blood 1990; 76: 538-48
- 25 Bertina RM, van Wijngaarden A, Reinalda-Poot J, Poort SR, Bom VJ J. Determination of plasma proteinS. The protein cofactor of activated protein C. Thromb Haemost 1985; 53: 268-72
- 26 Saiki RK, Schaaf S, Falvona F, Mnllis KR, Horn GT, Fbrlirh HA, Arnhiem N. Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of ridde cell uiiuemiu. Science 1985; 23: 1350-4
- 27 Sanger F, Nicklen S, Coulsen AR. DNA sequencing with chain terminating inhibitions. Proc Natl Acad Sci USA 1977; 74: 5463-7
- 28 Ploos van Amstel HK, Reitsma PH, Hamulyak K, de Die-Smulders CE M, Manucci 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
- 29 Ploos van Amstel HK, Huisman MV, Reitsma PH, ten Cate JW, Bertina RM. Partial protein S gene deletion in a family with hereditary thrombophilia. Blood 1989; 73: 479-83
- 30 Schmidel DK, Nelson RM, Broxson EH, Comp PC, Marlar RA, Long GL. A 5.3' Kb deletion including exon XIII of the protein Sa gene occurs in two protein S deficient families. Blood 1991; 77: 55-9
- 31 Reitsma PH, Ploos van Amstel HK, Bertina RM. Three novel mutations in 5 unrelated subjects with hereditary protein S deficiency type I. J Clin Invest 1994; 93: 486-92
- 32 Gomez E, Reitsma PH, Bertina RM. Genetic characterization of protein S (PS) deficiencies type I. Blood 1992; 80: 1-1056 (Abstr.)
- 33 Gandrille S, Borgel D, Gouault-Heilmann M, Dreyfus M, Aiach M. Identification of two punctual mutations in the protein S alpha gene of subjects with quantitative deficiency. Circulation 1992; 86: 1-3240 (Abstr.)
- 34 Marlar RA, Montgomery RR. Broekmans AW and the Working Party: Diagnosis and treatment of homozygous protein C deficiency. J Pediatr 1989; 114: 528-34
- 35 Grundy CB, Melissary E, Lindo V, Scully MF, Kakkar V, Cooper DN. Late-onset homozygous protein C deficiency. The Lancet 1991; 338: 575-6
- 36 Conard J, Horellou MH, Dreden P van, Samama M, Reitsma PH, Poort S, Bertina RM. Homozygous protein C deficiency with late onset and recurrent coumarin-induced skin necrosis. The Lancet 1992; 339: 743-1