Thromb Haemost 1995; 73(05): 876-889
DOI: 10.1055/s-0038-1653885
Scientific and Standardization Committee Communications
Schattauer GmbH Stuttgart

Protein C Deficiency: A Database of Mutations, 1995 Update

On behalf of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardization Committee of the ISTH
P H Reitsma
1   the hemostasis and Thrombosis Research Center, University Hospital, Leiden, The Netherlands
,
F Bernardi
2   Dipartimento Biochimica e Biologia Moleculare, Università degli studi di Ferrara, Ferrara, Italy
,
R G Doig
3   Diagnostic Haematology, The Royal Melbourne Hospital, Victoria, Australia
,
S Gandrille
4   INSERM CJF 91-01, UFR des Sciences Pharma- ceutiques et Biologiques, Paris, France
,
J S Greengard
5   Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA
,
H Ireland
6   Department of Haematology, Charing Cross & Westminster Medical School, London, UK
,
M Krawczak
7   Abteilung Humangenetik, Medizinische Hochschule, Hannover, Germany
,
B Lind
8   Section for Hemostasis and Thrombosis, Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
,
G L Long
9   Department of Biochemistry, School of Medicine, University of Vermont, Burlington, VT, USA
,
S R Poort
1   the hemostasis and Thrombosis Research Center, University Hospital, Leiden, The Netherlands
,
H Saito
10   First Department of Internal Medicine, Nagoya University School of Medicine, Tsurumai-cho, Nagoya, Japan
,
N Sala
11   Cancer Research Institute, Hospital Duran I Reynals, Barcelona, Spain
,
I Witt
12   Biochemisches Labor, Universitäts-Kinderklinik Freiburg, Freiburg, Germany
,
D N Cooper
13   Charter Molecular Genetics Laboratory, Thrombosis Research Institute, London, UK
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
09. Juli 2018 (online)

 
  • References

  • 1 Esmon CT. Molecular events that control the protein C anticoagulant pathway. Thromb Haemost 1994; 70: 29-35
  • 2 Dahlbäck B, Stenflo J. A natural anticoagulant pathway: proteins C, S, C4b-binding protein and thrombomodulin. In: Haemostasis and Thrombosis. Bloom AL, Forbes CD, Thomas DP, Tuddenham EG D. eds Edinburgh: Churchill Livingstone; 1994. pp 671-698
  • 3 Tuddenham EG D, Cooper DN. The molecular genetics of haemostasis and its inherited disorders. Oxford: Oxford University Press; 1994
  • 4 Foster D, Davie EW. Characterization of a cDNA coding for human protein C. Proc Natl Acad Sci USA 1984; 81: 4766-4770
  • 5 Beckmann RJ, Schmidt RJ, Santerre RF, Plutzky J, Crabtree GR, Long GL. The structure and evolution of a 461 amino acid human protein C precursor and its messenger RNA, based upon the DNA sequence of cloned human liver cDNAs. Nucleic Acids Res 1985; 13: 5233-5247
  • 6 Foster DC, Yoshitake S, Davie EW. The nucleotide sequence of the gene for human protein C. Proc Natl Acad Sci USA 1985; 82: 4673-4677
  • 7 Plutzky J, Hoskins JA, Long GL, Crabtree GR. Evolution and organization of the human protein C gene. Proc Natl Acad Sci USA 1986; 83: 546-550
  • 8 Patracchini P, Aiello V, Palazzi P, Calzolari E, Bernardi F. Sublocalization of the human protein C gene on chromosome 2ql3-ql4. Hum Genet 1989; 81: 191-192
  • 9 Reitsma PH, Poort SR, Bernardi F, Gandrille S, Long GL, Sala N, Cooper DN. Protein C deficiency: a database of mutations. Thromb Haemost 1993; 69: 77-84
  • 10 Spek CA, Poort SR, Bertina RM, Reitsma PH. Determination of the allelic and haplotype frequences of three polymorphisms in the promoter region of the human protein C gene. Blood Coagul Fibrinolysis 1994; 5: 309-311
  • 11 Tsay W, Greengard JS, Griffin JH. Exonic polymorphisms in the protein C gene: interethnic comparison between Caucasians and Asians. Hum Genet 1994; 94: 177-178
  • 12 Long GL, Belagaje RM, MacGillivray RT. Cloning and sequencing of liver cDNA coding for bovine protein C. Proc Natl Acad Sci US A 1984; 81: 5653-5656
  • 13 Okafuji T, Maekawa K, Nawa K, Marumoto Y. The cDNA cloning and mRNA expression of rat protein C. Biochim Biophys Acta 1992; 1131: 329-332
  • 14 Tada N, Sato M, Tsujimura A, Iwase R, Hashimoto-Gotoh T. Isolation and characterization of a mouse protein C cDNA. J Biochem (Tokyo) 1992; 111: 491-495
  • 15 Murakawa M, Okamura T, Kamura T, Kuroiwa M, Harada M. A comparative study of partial primary structures of the catalytic region of mammalian protein C. Br J Haematol 1994; 86: 590-600
  • 16 Broekmans AW, Conard J. Hereditary protein C deficiency. In: Protein C and related proteins. Bertina RM. ed Edinburgh: Churchill Livingstone; 1988. pp 160-181
  • 17 Gladson CL, Scharrer I, Hach V, Beck KH, Griffin JH. The frequency of type I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis. Thromb Haemost 1988; 59: 18-22
  • 18 Miletich J, Sherman L, Broze Jr G. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 317: 991-996
  • 19 Bovill EG, Bauer KA, Dickerman JD, Callas P, West B. The clinical spectrum of heterozygous protein C deficiency in a large New England kindred. Blood 1989; 73: 712-717
  • 20 Allaart CF, Poort SR, Rosendaal FR, Reitsma PH, Bertina RM, Briët E. Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect. Lancet 1993; 341: 134-138
  • 21 Henkens CM A, Van derMeer, Hillege JL, Van derSchaaf, Bom VJ, Halie MR. The clinical expression of hereditary protein C and protein S deficiency: a relation to clinical thrombotic risk factors and to levels of protein C and protein S. Blood Coagul Fibrinolysis 1993; 4: 555-562
  • 22 Mannucci PM, Vigano S, Bottasso B, Candotti G, Bozzetti P, Rossi E, Pardi G. Protein C antigen during pregnancy, delivery and puerperium. Thromb Haemost 1984; 52: 217
  • 23 Meade TW, Stirling Y, Wilkes H, Mannucci PM. Effects of oral contraceptives and obesity on protein C antigen. Thromb Haemost 1985; 53: 198-199
  • 24 Bertina RM, Koeleman BP C, Koster T, Rosendaal FR, Dirven RJ, De RondeH, Van derVelden, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 364-7
  • 25 Koeleman BP C, Reitsma PH, Allaart CF, Bertina RM. APC-resistance as an additional risk factor for thrombosis in protein C deficient families. Blood 1994; 84: 1031-1035
  • 26 Marlar RA, Montgomery RR, Broekmans AW. Diagnosis and treatment of homozygous protein C deficiencyReport of the working party on homozygous protein C deficiency of the subcommittee on protein C and protein S, International Committee on Thrombosis and Haemostasis. J Pediatr 1989; 114: 528-534
  • 27 Tuddenham EG, Takase T, Thomas AE, Awidi AS, Madanat FF, Abu HajirM, Kernoff PB, Hoffbrand AV. Homozygous protein C deficiency with delayed onset of symptoms at 7 to 10 months. Thromb Res 1989; 53: 475-484
  • 28 Wacey AI, Pemberton S, Cooper DN, Kakkar VV, Tuddenham EG D. A molecular model of the serine protease domain of activated protein C: application to the study of missense mutations causing protein C deficiency. Br J Haematol 1993; 84: 290-300
  • 29 Greengard JS, Fisher CL, Villoutreix B, Griffin JH. Structural basis for type I and type II déficiences of antithrombotic plasma protein C: patterns revealed by three-dimensional molecular modeling of mutations of the protease domain. Proteins: Struct Func Genet 1994; 18: 367-380
  • 30 Marchetti G, Patracchini P, Gemmati D, Castaman G, Rodeghiero F, Wacey A, Cooper DN, Tuddenham EG, Bernardi F. Symptomatic type II protein C deficiency caused by a missense mutation (GlyySer) in the substrate-binding pocket of serine proteases. Br J Haematol 1993; 84: 285-289
  • 31 Cooper DN, Krawczak M. Human gene mutation. Oxford: Bios Scientific; 1994
  • 32 Lind B, Van SolingeW, Schwartz M, Thorsen S. Splice site mutation in the human protein C gene associated with venous thrombosis: Demonstration of exon skipping by ectopic transcript analysis. Blood 1993; 82: 2423-2432
  • 33 Berg L-P, White DA, Alhaq A, Kakkar VV, Cooper DN. Disruption of a binding site for hepatocyte nuclear factor 1 (HNF-1) in the protein C (PROC) gene promoter is associated with hereditary thrombophilia. Hum Mol Genet 1994; 3: 2147-2152
  • 34 Matsuda M, Sugo T, Sakata Y, Murayama H, Mimuro J, Tanabe S, Yoshi-take S. A thrombotic state due to an abnormal protein C. N Engl J Med 1988; 319: 1265-1268
  • 35 Krawczak M, Reitsma PH, Cooper DN. The mutational demography of protein C deficiency. Hum Genet. 1995 (in press)
  • 36 Greengard JS, Tsay W, Montgomery R, Heeb MJ, Griffin JH. 1994 Personal communication.
  • 37 Poort SR, Pabinger-Fasching I, Mannhalter C, Reitsma PH, Bertina RM. Twelve novel and two recurrent mutations in 14 Austrian families with hereditary protein C deficiency. Blood Coagul Fibrinolysis 1993; 4: 273-280
  • 38 Millar DS, Grundy CB, Bignell P, Mitchell DC, Corden D, Woods P, Kakkar VV, Cooper DN. A novel nonsense mutation in the protein C gene (Trp-29-Term) causing recurrent venous thrombosis. Hum Genet 1993; 91: 196
  • 39 Soria JM, Sala N. 1994 Personal communication.
  • 40 Tomczak JA, Broxson EH, Marlar RA, Long GL. Association of two novel intron mutations with familial type one protein C deficiency. Thromb Haemost 1993; 69: 721 (Abstract)
  • 41 Tait RC, Walker ID, Reitsma PH, Islam SI A M, McCall F, Poort SR, Conkie JA, Bertina RM. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995; 73: 87-93
  • 42 Zheng YZ, Sakata T, Matsusue T, Umeyama H, Kato H, Miyata T. Six missense mutations associated with type I and type II protein C deficiency and implications obtained from molecular modeling. Blood Coagul Fibrinolysis 1994; 5: 687-696
  • 43 Gandrille S, Aiach M. and the French INSERM Network on “the Molecular Basis of Protein C and Protein S hereditary deficiencies”. 1994 Personal communication
  • 44 Millar DS, Cooper DN. 1994 Personal communication.
  • 45 Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-1373
  • 46 Long GL. 1994 Personal communication.
  • 47 Ireland H, Thompson E, Taylor J, Boisclair MD, Lane DA, Girolami A, De-Caterina M, DeStefano V, Leone G, Finazzi G, Cohen H. Molecular basis of protein C deficiency in five families with thrombophilia. Blood Coagul Fibrinolysis 1993; 4: 351 (Abstract)
  • 48 Ireland H, Lane DA. 1994 Personal communication.
  • 49 Gandrille S, Vidaud M, Aiach M, Alhenc-Gelas M, Fischer AM, Gouault-Heilmann M, Toulon P, Fiessinger JN, Goossens M. Two novel mutations responsible for type I protein C deficiency: characterization by denaturing gradient gel electrophoresis. Hum Mut 1993; 1: 491-500
  • 50 Sala N, Poort SR, Bertina RM, Soria JM, Fontcuberta J, Reitsma PH. Identification of two deletions and four point mutations in the protein C gene of 6 unrelated Spanish patients with hereditary protein C deficiency. Thromb Haemost 1991; 65: 1197 (Abstract)
  • 51 Gandrille S, Alhenc-Gelas M, Aillaud MF, Dupuy E, Aiach M. Protein C hereditary qualitative deficiency due to an arginine -1 to cysteine mutation in propeptide. Circulation 1992; 86: 2934 (Abstract)
  • 52 Girolami A, Simioni P, Girolami B, Marchiori A, Millar DS, Bignell P, Kakkar VV, Cooper DN. A novel dysfunctional protein C (protein C Padua 2) associated with a thrombotic tendency: substitution of Cys for Arg-1 results in a strongly reduced affinity for binding of Ca++ . Br J Haematol 1993; 85: 521-527
  • 53 Gandrille S, Alhenc-Gelas M, Goossens M, Aiach M, Malakoff PC. An abnormal protein C due to mutation at the cleavage site of the propeptide. Thromb Haemost 1991; 65: 1196 (Abstract)
  • 54 Lind B, Schwartz M, Thorsen S. Six different missense mutations in seven Danish families with symptomatic protein C deficiency. Thromb Haemost 1993; 69: 2540 (Abstract)
  • 55 Poort SR, Bertina RM, Reitsma PH. 1994 Personal communication.
  • 56 Gandrille S, Vidaud M, Aiach M, Alhenc-Gelas M, Fischer AM, Gouault-Hellman M, Toulon P, Goossens M. Six previously undescribed mutations in 9 families with protein C quantitative deficiency. Thromb Haemost 1991; 65: 646 (Abstract)
  • 57 Mimuro J, Matsumura S, Kaneko M, Yoshitake S, Iijima K, Nakamura K, Sakata Y, Matsuda M. An abnormal protein C (protein C Yonago) with an amino acid substitution of Gly for Arg-15 caused by a single base mutation of C to G in codon 57 (CGG-→GGG): detoriated calcium-dependent conformation of the Γ-carboxy-glutamic acid domain relative to thrombotic tendency. Int J Haematol 1993; 57: 9-14
  • 58 Bovill EG, Tomczak JA, Grant B, Bhushan F, Pillemer E, Rainville IR, Long GL. Protein CVermont: Symptomatic type II protein C deficiency associated with two GLA domain mutations. Blood 1992; 79: 1456-1465
  • 59 Greengard JS, Tsay W, Vicente V, Griffin JH. 1994 Pers.comm.
  • 60 Ido M, Ohiwa M, Hayashi T, Nishioka J, Hatada T, Watanabe Y, Wada H, Shirakawa S, Suzuki K. A compound heterozygous protein C deficiency with a single nucleotide G deletion encoding Gly-381 and an amino acid substitution of Lys for Gla-26. Thromb Haemost 1993; 70: 636-641
  • 61 Koster T, Rosendaal FR, Van der Meer FJ M, Colly LP, Trienekens PH, 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 (in press)
  • 62 Soria JM, Fontcuberta J, Borrell M, Estivill X, Sala N. Two novel mutations in exon 5 of the protein C gene in two Spanish families with thrombophilia due to protein C deficiency. Hum Mol Genet 1994; 3: 1205-1206
  • 63 Tsay W, Greengard JS, Montgomery R, Griffin JH. Five previously undescribed mutations in protein C (PC) that identify elements critical for gene and protein activity. Blood 1991; 78: 184a (Abstract)
  • 64 Poort SR, Reitsma PH. 1994 Personal communication.
  • 65 Witt I. 1994 Personal communication.
  • 66 Reitsma PH, Poort SR, Allaart CF, Briët E, Bertina RM. The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: Heterogeneity and founder effects. Blood 1991; 78: 890-894
  • 67 Tsuda S, Reitsma PH, Miletich J. Molecular defects causing heterozygous protein C deficiency in three asymptomatic kindreds. Thromb Haemost 1991; 65: 647 (Abstract)
  • 68 Sala N, Soria JM, Borrell M, Navarro G, Fontcuberta J, Estivill X. Estudio de la mutacion causante del deficit cualitativo de PC en tres familias. Sangre 1993; 38: 20 (Abstract)
  • 69 Doig RG. 1994 Personal communication.
  • 70 Soria JM, Fontcuberta J, Chillón M, Borrell M, Estivill X, Sala N. Acceptor splice site mutation in the invariant AG of intron 5 of the protein C gene, causing type I protein C deficiency. Hum Genet 1993; 92: 506-508
  • 71 Tomczak JA, Ando RA, Sobel HG, Bovill EG, Long GL. Genetic analysis of a large kindred exhibiting type I protein C deficiency and associated thrombosis. Thromb Res 1994; 74: 243-54
  • 72 Estelles A, Garcia PlazaI, Dasi A, Aznar J, Duart M, Sanz G, Perez RequejoJ, Espana F, Jimenez C, Abeledo G. Severe inherited “homozygous” protein C deficiency in a newborn infant. Thromb Haemost 1984; 52: 53-56
  • 73 Sugahara Y, Miura O, Yuen P, Aoki N. Protein C deficiency Hong Kong 1 and 2: Hereditary protein C deficiency caused by two mutant alleles, a 5-nucleotide deletion and a missense mutation. Blood 1992; 80: 126-133
  • 74 Dreyfus M, Magny JF, Bridey F, Schwarz HP, Planch C, Dehan M, Tchemia G. Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med 1991; 325: 1565-1568
  • 75 Long GL, Tomczak JA, Rainville IR, Dreyfus M, Schramm W, Schwarz HP. Homozygous protein C deficiency in two unrelated families exhibiting thrombophilia related to Alal366Pro or Arg2868His mutations. Thromb Haemost 1994; 72: 526-533
  • 76 Witt I, Seydewitz HH, Asbeck D, Beck S, Nabel C. Protein C gene mutations in ten unrelated families with symptomatic protein C deficiency. Ann Hematol 1994; 68: 58 (Abstract)
  • 77 Soria JM, Fontcuberta J, Borrell M, Estivill X, Sala N. Protein C deficiency: identification of a novel two-base pair insertion and two point mutations in exon 7 of the protein C gene in Spanish families. Hum Mut 1992; 1: 428-431
  • 78 Grundy C, Plendl H, Grote W, Zoll B, Kakkar VV, Cooper DN. A single base-pair deletion in the protein C gene causing recurrent thromboembolism. Thromb Res 1991; 61: 335-340
  • 79 Gandrille S, Vidaud M, Aiach M, Alhenc-Gelas M, Fischer AM, Gouault-Hellman M, Toulon P, Goossens M. Quantitative hereditary protein C deficiency: identification of two novel mutations at CpG sites in exon VI of the protein C gene. Blood 1990; 76: 2018 (Abstract)
  • 80 Conard J, Horellou MH, Van DredenP, Samama M, Reitsma PH, Poort SR, Bertina RM. Homozygous protein C deficiency with late onset and recurrent coumarin-induced skin lesions. Lancet 1992; 339: 743-744
  • 81 Nesbitt IM, Winship PR, Preston FE, Peake IR. Mutation at the thrombin activation site of protein C in a protein C deficient family. Proc 24th Int Soc Haematol; London: 1992: 40 (Abstract)
  • 82 Grundy C, Chitolie A, Talbot S, Bevan D, Kakkar V, Cooper DN. Protein C London 1: recurrent mutation at Arg 169 (CGG-TGG) in the protein C gene causing thrombosis. Nucleic Acids Res 1989; 17: 10513
  • 83 Grundy CB, Schulman S, Tengbom L, Kakkar VV, Cooper DN. Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis. Hum Genet 1992; 89: 685-686
  • 84 Hertfelder H-J, Poort SR, Reitsma PH. 1994 Personal communication.
  • 85 Soria JM, Brito D, Barcelo J, Fontcuberta J, Botero L, Maldonado J, Estivill X, Sala N. Severe homozygous protein C deficiency: identification of a splice site missense mutation ( 184, QQH) in exon 7 of the protein C gene. Thromb Haemost 1994; 72: 65-69
  • 86 Sala N, Borrell M, Bauer KA, Vigano S, Fontcuberta J, Felez J, Rutilant ML. Dysfunctional activated protein C (PC Cadiz) in a patient with thrombotic disease. Thromb Haemost 1987; 57: 183-186
  • 87 Soria JM, Fontcuberta J, Brito D, Estivill X, Sala N. The use of SSCP’s in the analysis of the protein C gene: identification of six different mutations in protein C deficient Spanish families. Thromb Haemost 1993; 69: 720 (Abstract)
  • 88 Gandrille S, Jude B, Alhenc-Gelas M, Milaire A, Aiach M. Compound heterozygosity in a family with quantitative protein C deficiency due to the association of Leu 223 to Phe and lie 403 to Met mutations. Thromb Haemost 1993; 69: 1281 (Abstract)
  • 89 Gandrille S, Alhenc-Gelas M, Juhan-Vague I, Fiessinger JN, Goossens M, Aiach M. Two qualitative protein C (PC) deficiencies due to Arg29→Gln (PC Marseille) and Ser252-→Asn (PC Paris) mutations. Thromb Haemost 1991; 65: 1196 (Abstract)
  • 90 Broekmans AW, Veltkamp JJ, Bertina RM. Congenital protein C deficiency and venous thromboembolismA study of three Dutch families. N Engl J Med 1983; 309: 340-344
  • 91 Bertina RM, Broekmans AW, van der Linden IK, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemost 1982; 48: 1-5
  • 92 Grundy CB, Melissari E, Lindo V, Scully MF, Kakkar VV, Cooper DN. Late-onset homozygous protein C deficiency. Lancet 1991; 338: 575-576
  • 93 Gandrille S, Alhenc-Gelas M, Emmerich J, Fiessinger JN, Aiach M. A de novo mutation responsible for type I protein C deficiency. Thromb Haemost 1993; 69: 1282 (Abstract)
  • 94 Yamamoto K, Matsushita T, Sugiura I, Takamatsu J, Iwasaki E, Wada H, Deguchi K, Shirakawa S, Saito H. Homozygous protein C deficiency: Identification of a novel missense mutation that causes impaired secretion of the mutant protein C. J Lab Clin Med 1992; 119: 682-689
  • 95 Millar DS, Wacey AI, Voke J, Kakkar VV, Cooper DN. A novel point mutation (Val 2977Met) in the serine proteinase domain of protein C in a patient with both venous and arterial thromboembolic disease. Blood Coagul Fibrinolysis 1993; 4: 631-633
  • 96 Bemardi F, Patracchini P, Gemmati D, Boninsegna S, Guerra S, Legnani C, Ballerini G, Marchetti G. Rapid detection of a protein C mutation present in the asymptomatic and not in the thrombosis-prone lineage. BrJ Haematol 1992; 81: 277-282
  • 97 Romeo G, Hassan HJ, Staempfli S, Roncuzzi L, Cianetti L, Leonardi A, Vicente V, Mannucci PM, Bertina R, Peschle C. et al Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene. Proc Natl Acad Sci USA 1987; 84: 2829-2832
  • 98 Grundy CB, Schulman S, Krawczak M, Kobosko J, Kakkar VV, Cooper DN. Protein C deficiency and thromboembolism: Recurrent mutation at Arg 306 in the protein C gene. Hum Genet 1992; 88: 586-588
  • 99 Gandrille S, Alhenc-Gelas M, Gaussem P, Aillaud M-F, Dupuy E, Juhan-Vague I, Aiach M. Five novel mutations located in exons III and IX of the protein C gene in patients presenting with defective protein C anticoagulant activity. Blood 1993; 82: 159-168
  • 100 Witt I, Seydewitz HH, Tasangil C, Schenk W. A novel homozygous missense mutation (Val3255Ala) in the protein C gene causing neonatal purpura fulminans. Blood Coagul Fibrinolysis 1994; 5: 651-653
  • 101 Yamamoto K, Tanimoto M, Emi N, Matsushita T, Takamatsu J, Saito H. Impaired secretion of the elongated mutant of protein C (protein C-Nagoya); molecular and cellular basis for hereditary protein C deficiency. J Clin Invest 1992; 90: 2439-2446
  • 102 Tokunaga F, Wakabayashi S, Sato H, Arakawa M, Tawaraya H, Koide T. Identification of one base deletion in exon IX of the protein C gene that causes a type I deficiency. Thromb Res 1992; 68: 417-423
  • 103 Miyata T, Zheng YZ, Sakata T, Tsushima N, Kato H. Three missense mutations in the protein C heavy chain causing type I and type II protein C deficiency. Thromb Haemost 1994; 71: 32-37
  • 104 Gonzalez R, Alberca I, Sala N, Vicente V. Protein C deficiency -response to danazol and DDAVP. Thromb Haemost 1985; 53: 320-322
  • 105 Gandrille S, Jude B, Alhenc-Gelas M, Millaire A, Aiach M. Compound heterozygosity in a family with protein C deficiency illustrating the complexity of the underlying molecular mechanism. Thromb Haemost 1993; 70: 747-752
  • 106 Bertina RM, Broekmans AW, Krommenhoek van Es C, van Wijngaarden A. The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency. Thromb Haemost 1984; 51: 1-5
  • 107 Sala N, Owen WG, Collen D. A functional assay of protein C in human plasma. Blood 1984; 63: 671-675
  • 108 Gaussem P, Gandrille S, Duchemin J, Alhenc-Gelas M, Aillaud MF, Aiach M. Influence of six mutations of the protein C gene on the GLA domain conformation and calcium affinity. Thromb Haemost 1994; 71: 748-754
  • 109 Gandrille S, Goossens M, Aiach M. A scanning method to establish the molecular basis of protein C deficiencies. Human Mutation 1994; 4: 20-30
  • 110 Gandrille S, Jude B, Alhenc-Gelas M, Emmerich J, Aiach M. First de novo mutations in two patients with type I deficiency: a missense mutation and a splice site deletion. Blood 1994; 84: 2566-2570
  • 111 Millar DS, Grundy CB, Bignell P, Moffat EH, Martin R, Kakkar VV, Cooper DN. A Gla domain mutation (Argl5_Trp) in the protein C gene causing type 2 protein C deficiency and recurrent venous thrombosis. Blood Coagul Fibrinolysis 1993; 4: 345-347
  • 112 Millar DS, Allgrove J, Rodeck C, Kakkar VV, Cooper DN. A homozygous deletion/insertion mutation in the protein C (PROC) gene causing neonatal purpura fulminans in an at-risk pregnancy. Blood Coagul Fibrinolysis 1994; 5: 647-679