Antithrombin Mutation Database: 2nd (1997) Update

D A Lane; T Bayston; R J Olds; A C Fitches; D N Cooper; D S Millar; K Jochmans; D J Perry; K Okajima; S L Thein; J Emmerich

doi:10.1055/s-0038-1655930

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1997; 77(01): 197-211
DOI: 10.1055/s-0038-1655930

Scientific and Standardization Committee Communication

Schattauer GmbH Stuttgart

Antithrombin Mutation Database: 2nd (1997) Update

For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis

Authors

D A Lane

¹The Charing Cross and Westminster Medical School, London, UK
T Bayston

¹The Charing Cross and Westminster Medical School, London, UK
R J Olds

²The University of Otago, Dunedin, New Zealand
A C Fitches

²The University of Otago, Dunedin, New Zealand
D N Cooper

³The Institute of Medical Genetics, Cardiff, UK
D S Millar

³The Institute of Medical Genetics, Cardiff, UK
K Jochmans

⁴The Free University Hospital Brussels, Belgium
D J Perry

⁵The Royal Free Hospital and School of Medicine, London, UK
K Okajima

⁶The Kumamoto University Medical School, Japan
S L Thein

⁷The Institute of Molecular Medicine, Oxford, UK
J Emmerich

⁸The Université René Descartes, Paris, France

Abstract

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Referenzen

References
1 Abildgaard U. Highly purified antithrombin III with heparin cofactor activity prepared by disc gel electrophoresis. Scandanavian Journal of Clinical and Laboratory Investigation 1968; 21: 89-91
2 Abildgaard U. Binding of thrombin to antithrombin III. Scandinavian Journal of Clinical and Laboratory Investigation 1969; 24: 23-27
3 Rosenberg RD, Damus PS. The purification and mechanism of action of human antithrombin-heparin cofactor. Journal of Biological Chemistry 1973; 248: 6490-6505
4 Lane DA, Ireland H, Olds RJ, Thein SL, Perry DJ, Aiach M. Antithrombin III: a database of mutations. Thromb Haemost 1991; 66: 657-661
5 Lane DA, Olds RJ, Boisclair M, Chowdhury V, Thein SL, Cooper DN, Blajchman M, Perry D, Emmerich J, Aiach M. Antithrombin III mutation database: first update. Thromb Haemost 1993; 70: 361-369
6 Blombäck M, Abildgaard U, van den Besselaar AMPH, Clemetson KJ, Dahlbäck B, Exner T, Francis CW, Gaffney PJ, Gralnick H, Hoyer LW, Johnson GJ, Kasper C, Lane DA, Lijnen HR, Luscher JM, Mannucci PM, Poller L, Rapaport SI, Saito H, Stocker K, Thomas D. Nomenclature of quantities and units in Thrombosis and Hameostasis (ISTH/SSC Recommendation 1993). Thromb Haemost 1994; 71: 375-394
7 Huber R, Carrell RW. Implications of the three dimensional structure of α₁ antitrypsin for structure and function of serpins. Biochemistry 1989; 28: 8951-8966
8 Bock SC, Harris JF, Balazs I, Trent JM. Assignment of the human anti-thrombin III structural gene to chromosome lq 23-25. Cytogenetics Cell Genetics 1985; 39: 67-69
9 Björk I, Danielsson A, Fenton JW, Jomvall H. The site in human antithrombin for functional proteolytic cleavage by human thrombin. Federation of European Biochemical Societies Letters 1981; 126: 257-260
10 Björk I, Jackson CM, Jomvall H, Lavine KK, Nording K, Salsgiver WJ. The active site of antithrombin. Release of the same proteolytically cleaved form of the inhibitor from complexes with Factor IXa, Factor Xa and thrombin. J Biol Chemistry 1982; 257: 2406-2411
11 Gettins PGW, Fan B, Crews BC, Turko IV, Olson ST, Streusand VJ. Transmission of conformational change from the heparin binding site to the reactive centre of antithrombin. Biochemistry 1993; 32: 8385-8389
12 Dawes J, James K, Lane DA. The conformational change in antithrombin induced by heparin, probed with a monoclonal antibody against the 1C/4B region. Biochemistry 1994; 33: 4375-4383
13 Screuder HA, de Boer B, Dijkema R, Mulders J, Theunissen HJM, Groo-tenhuis PDJ, Hoi WGJ. The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions. Nature Structural Biology 1994; 01: 48-54
14 Carrell RW, Stein PE, Fermi G, Wardell MR. Biological implications of a 3A structure of dimeric antithrombin. Structure 1994; 02: 257-270
15 Chang JY. Binding of heparin to antithrombin III activates selective chemical modification at lysine 236 Lys-107, Lys-125 and Lys-136 are situated within the heparin binding site of antithrombin III. J Biol Chemistry 1989; 264: 3111-3115
16 Liu CS, Chang JY. Probing the heparin binding domain of human antithrombin III with V8 protease. Eur J Biochemistry 1987; 167: 247-252
17 Liu CS, Chang JY. The heparin binding site of human antithrombin III. Selective chemical modification at Lys 114, Lys 125 and Lys 287 impairs its heparin cofactor activity. J Biol Chemistry 1987; 262: 17356-17361
18 Fan B, Turko IV, Gettins PGW. Lysine-heparin interactions in antithrombin Properties of K125M and K290M, K294M, K297M variants. Biochemistry 1994; 33: 14156-14161
19 Fan B, Turko IV, Gettins PGW. Antithrombin histidine variants 1H NMR resonance assignments and functional properties. Federation of European Biochemical Societies Letters 1994; 354: 84-88
20 Egberg O. Inherited antithrombin III deficiency causing thrombophilia. Thrombosis et Diathesis Haemorrhagica 1965; 13: 516-530
21 Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. Clinics in Haematology 1981; 10: 369-390
22 Demers C, Ginsberg JS, Hirsh J, Henderson P. Thrombosis in antithrom-bin-III-deficient persons Report of a large kindred and literature review. Annals of Internal Medicine 1992; 116: 754-761
23 Rosendaal FR, Heijboer H, Briët E, Büller H, Brandjes DPM, De Bruin K, Hommes DW, Vandenboucke JP. Mortality in hereditary antithrombin III deficiency – 1830-1989. Lancet 1991; 337: 260-262
24 van Boven HH, Olds RJ, Thein SL, Reitsma PH, Lane DA, Briët E, Van-denbroucke JP, Rosendaal FR. Hereditary antithrombin deficiency: heterogeneity of the molecular basis and mortality in Dutch families. Blood 1994; 84: 4209-4213
25 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterised by poor anticoagulant response to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-1008
26 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden P, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67
27 van Boven HH, Reitsma PH, Rosendaal FR, Bayston TA, Chowdhury V, Bauer K, Scharrer I, Conard J, Lane DA. Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency. Thromb Haemost 1996; 75: 417-421
28 Rosenberg RD. Actions and interactions of antithrombin and heparin. N Engl J Med 1975; 292: 146-151
29 Abildgaard U. Antithrombin and related inhibitors of coagulation. In: Recent advances in blood coagulation. Poller L. (ed) Churchill Livingstone, Edinburgh. 1981. pp 151-173
30 Tait RC, Walker ID, Perry DJ, Carrell RW, Islam SIA, McCall F, Mitchell R, Davidson JF. Prevalence of antithrombin III deficiency subtypes in 4000 healthy blood donors. Thromb Haemost 1991; 65: 839
31 Tait RC, Walker ID, Islam SIA, McCall F, Conkie JA, Mitchell R, Davidson JF. Influence of demographic factors on antithrombin III activity in a healthy population. British Journal of Haematology 1993; 84: 476-480
32 Sas G, Banhegyi D, Blasko G, Domjam G. Heterogeneity of the “classical” antithrombin III deficiency. Thromb Haemost 1980; 43: 133-136
33 Sas G. Hereditary antithrombin III deficiency: biochemical aspects. Hae-matologia 1984; 07: 81-86
34 Hultin MB, McKay J, Abildgaard U. Antithrombin Oslo: Type lb classification of the first reported antithrombin-deficient family with a review of the hereditary antithrombin variants. Thromb Haemost 1988; 59: 468-473
35 Finazzi G, Caccia R, Barbui T. Different prevalence of thromboembolism in the subtypes of congenital antithrombin III deficiency: review of 404 cases. Thromb Haemost 1987; 58: 1094
36 Ireland H, Bayston TA, Chowdhury V, Thein SL, Conard J, Pabinger I, Lane DA. Factor V Leiden as an independent risk factor in antithrombin deficiency type II: heparin binding site. 1996. In preparation
37 Prochownik EV. Relationship between an enhancer element in the human antithrombin III gene and an immunoglobulin light-chain gene enhancer. Nature 1985; 316: 845-848
38 Ochoa A, Brunei F, Mendelzon D, Cohen GN, Zakin MM. Different liver nuclear proteins bind to similar DNA sequences in the 5’ flanking regions of three hepatic genes. Nucleic Acids Research 1989; 17: 119-133
39 Nieseen R, Rezaee F, de Vijlder J, Sturk A. Human antithrombin III gene expression is probably regulated by a hormone receptor response element. Thromb Haemost 1995; 73: 1343 (abstract 1342)
40 Rosenberg J, Bergtrom G, Amrani D. Identification of FXP1 and LF1 regulatory sites in the 5’ upstream region of the human antithrombin gene. Thromb Haemost 1995; 73: 1249 (abstract 1335)
41 Tremp GL, Duchange N, Branellec D, Cereghini S, Tailleux A, Berthou L, Fievet C, Touchet N, Schombert B, Fruchart J-C, Zakin MM, Denefle P. A 700-bp fragment of the human antithrombin III promoter is sufficient to confer high, tissue-specific expression on human apolipoprotein A-II in transgenenic mice. Gene 1995; 156: 199-205
42 Winter PC, Scopes DA, Berg L-P, Millar DS, Kakkar VV, Mayne EE, Krawczak M, Cooper DN. Functional analysis of an unusual length polymorphism in the human antithrombin III (AT3) gene promoter. Blood Coagul Fibrinol 1995; 6: 659-664
43 Olds RJ, Lane DA, Chowdhury V, De Stefano V, Leone G, Thein SL. Complete nucleotide sequence of the antithrombin gene. Evidence for homologous recombination causing thrombophilia. Biochemistry 1993; 32: 4216-4224
44 Bock SC, Marrinan JA, Radziejewska E. Antithrombin III Utah: proline 407 to leucine mutation in a highly conserved region near the inhibitor reactive site. Biochemistry 1988; 27: 6171-6178
45 Emmerich J, Vidaud D, Alhenc-Gelas M, Chadeuf G, Gouault-Heilmann M, Aillaud MF, Aiach M. Three novel mutations of antithrombin inducing high molecular mass compounds. Arteriosclerosis and Thrombosis 1994; 14: 1958-1965
46 Erdjument H, Lane DA, Panico M, diMarzo V, Morris HR. Single amino acid substitutions in the reactive site of antithrombin leading to thrombosis. Congenital substitution of arginine 393 to cysteine in antithrombin Northwick Park and to histidine in antithrombin Glasgow. J Biol Chemistry 1988; 263: 5589-5593
47 Lane DA, Erdjument H, Thompson E, Panico M, DiMarzo V, Morris HR, Leone G, De Stefano V, Thein SL. A novel amino acid substitution in the reactive site of a congenital variant antithrombin. Antithrombin Pescara, Arg 393 to Pro, caused by CGT to CCT mutation. J Biol Chemistry 1989; 264: 10200-10204
48 Blajchman MA, Femandez-Rachubinsky F, Sheffield WP, Austin RC, Schulman S. Antithrombin III Stockholm: a codon 392 (Gly to Asp) mutation with normal heparin binding and impaired serine protease reactivity. Blood 1992; 79: 1428-1434
49 Stephens AW, Thalley BS, Hirs CHW. Antithrombin Denver, a reactive site variant. J Biol Chemistry 1987; 262: 1044-1048
50 Erdjument H, Lane DA, Ireland H, Panico M, DiMarzo V, Blench I, Morris HR. Formation of a covalent disulfide-linked antithrombin complex by an antithrombin variant, antithrombin Northwick Park. J Biol Chemistry 1987; 262: 13381-13384
51 Lane DA, Flynn A, Ireland H, Erdjument H, Samson D, Howarth D, Thompson E. Antithrombin III Northwick Park: demonstration of a high MW complex with increased affinity for heparin. Brit J Haematol 1987; 65: 451-456
52 Lane DA, Lowe GDO, Flynn A, Thompson E, Ireland H, Erdjument H. Antithrombin III Glasgow: a variant with increased heparin affinity and reduced ability to inactivate thrombin, associated with familial thrombosis. Brit J Haematol 1987; 523: 523-527
53 Watton J, Longstaff C, Lane DA, Barrowcliffe TW. Heparin binding affinity of normal and genetically modified antithrombin III measured using a monoclonal antibody to the heparin binding site of antithrombin III. Biochemistry 1993; 32: 7286-7293
54 Caso R, Lane DA, Thompson EA, Olds RJ, Thein SL, Panico M, Blench I, Morris H, Freyssinet JM, Aiach M, Rodeghiero F, Finazzi G. Antithrombin Vicenza, Ala 384 to Pro (GCA to CCA) mutation transforming the inhibitor into a substrate. Brit J Haematol 1991; 77: 87-92
55 Ireland H, Lane DA, Thompson E, Walker ID, Blench I, Morris HR, Freyssinet JM, Grunebaun L, Olds R, Thein SL. Antithrombin Glasgow II: alanine to threonine mutation in the serpin P12 position, resulting in a substrate reaction with thrombin. Brit J Haematol 1991; 79: 70-74
56 Olson ST, Sheffer R, Stephens AW, Hirs CHW. Molecular basis of the reduced activity of antithrombin-Denver with thrombin and factor Xa. Role of the P’ 1 residue. Thromb Haemost 1991; 65: 670
57 Bruce D, Perry DJ, Borg J-Y, Carrell RW, Wardell MR. Thromboembolic disease due to thermolabile conformational changes of antithrombin Rouen VI (187 Asn to Asp). J Clin Investigation 1994; 94: 2265-2274
58 Koide T, Odani S, Takahashi K, Ono T, Sakuragawa N. Antithrombin III Toyama; replacement of Arginine 47 by Cysteine in hereditary abnormal antithrombin III that lacks heparin-binding ability. Proceedings of the National Academy of Science USA 1984; 81: 289-293
59 Gandrille S, Aiach M, Lane DA, Vidaud D, Mohlo-Sabatier P, Caso R, de Moerloose P, Fiessinger JN, Clauser E. Important role of Arg 129 in heparin binding site of antithrombin III: identification of novel mutation Arg 129 to Gin. J Biol Chemistry 1990; 265: 18997-19001
60 Borg JY, Brennan SO, Carrell RW, George P, Perry DJ, Shaw J. Anti-thrombin Rouen IV 24 Arg to Cys. The amino terminal contribution to heparin binding. Federation of European Biochemical Societies Letters 1990; 266: 163-166
61 Mille B, Watton J, Barrowcliffe TW, Mani JC, Lane DA. Role of N and C terminal amino acids in antithrombin binding to pentasaccharide. J Biol Chem 1994; 269: 29435-29443
62 Brennan SO, Borg JY, George PM, Soria C, Soria J, Caen J, Carrell RW. New carbohydrate site in mutant antithrombin (7IIe-Asn) with decreased heparin affinity. Federation of European Biochemical Societies Letters 1988; 237: 118-122
63 Lane DA, Olds RJ, Conard J, Boisclair M, Bock SC, Hultin M, Abildgaard U, Ireland H, Thompson E, Sas G, Horellou MH, Tamponi G, Thein SL. Pleiotropic effects of anti-thrombin strand 1C substitution mutations. J Clin Investigation 1992; 2422: 2422-2433
64 Olds RJ, Lane DA, Chowdury V, Sas G, Pabinger I, Auberger K, Thein SL. (ATT) trinucleotide repeats in the antithrombin gene and their use in determining the origin of repeated mutations. Human Mutation 1994; 04: 31-41
65 Csurgay E, Ireland H, Thompson E, Conard J, Mannucci PM, Andrews V, Worsley A, Sas G, Lane DA. Novel mutations in seven families with type I antithrombin deficiency. Thromb Haemost 1995; 73: 935
66 Daly M, Perry DJ, Bruce DB, Harper PL, Tait RC, Walker ID, Mayne EE, Daly HM, Brown K, Carrell RW. Type I antithrombin deficiency: 5 novel mutations associated with thrombosis. Blood Coagulation and Fibrinolysis. 1996. in press;
67 Daly ME, Perry DJ, Harper PL, Carrell RW. The molecular basis of quantitative antithrombin deficiency in 8 unrelated families. Brit J Haematol 1992; 80: 15
68 Daly M, Perry DJ, Harper PL, Daly HM, Roques AWW, Carrell RW. Insertions/deletions in the antithrombin gene: 3 mutations associated with non-expression. Thromb Haemost 1992; 67: 521-525
69 Chowdhury V, Olds RJ, Lane DA, Conard J, Pabinger I, Ryan K, Bauer K, Bhavani M, Abildgaard U, Finazzi G, Castaman G, Mannucci PM, Thein SL. Identification of nine novel mutations in type I antithrombin deficiency by heteroduplex screening. Brit J Haematol 1993; 84: 656-661
70 Millar DS, Wacey AI, Ribando J, Melissari E, Laursen B, Woods P, Kak-kar VV, Cooper DN. Three novel missense mutations in the antithrombin III (AT3) gene causing recurrent venous thrombosis. Human Genetics 1995; 94: 509-512
71 Olds RJ, Lane DA, Ireland H, Leone G, De Stefano V, Wiesel ML, Caze-nave JP, Thein SL. Novel point mutations leading to type I antithrombin deficiency and thrombosis. Brit J Haematol 1991; 78: 408-413
72 Perry DJ. Ectopic transcript analysis in human antithrombin deficiency. Blood Coagul Fibrinolysis 1995; 06: 531-536
73 Olds RJ, Lane DA, Beresford CH, Abildgaard U, Hughes PM, Thein SL. A recurrent deletion in the antithrombin gene, AT106-108(-6bp), identified by DNA heteroduplex detection. Genomics 1993; 16: 298-299
74 Millar DS, Lopez A, White D, Abraham G, Laursen B, Holding S, Reverter JC, Reynand J, Martinowitz U, Hayes JPLA, Kakkar VV, Cooper DN. Screening for mutations in the antithrombin III (AT3) gene causing recurrent venous thrombosis by single strand conformation polymorphism analysis. Human Mutation 1993; 02: 324-326
75 Olds RJ, Lane DA, Finazzi G, Barbui T, Thein SL. A frameshift mutation leading to type 1 antithrombin deficiency and thrombosis. Blood 1990; 76: 2182-2186
76 Gandrille S, Vidaud D, Emmerich J, Clauser E, Sié P, Fiessinger JN, Alhenc-Gelas M, Priollet P, Aiach M. Molecular basis for hereditary anti-thrombin III quantitative deficiencies: a stop codon in exon IIIa and a frameshift in exon V1. Brit J Haematol 1991; 78: 414-420
77 Olds RJ, Lane DA, Ireland H, Finazzi G, Barbui T, Abildgaard U, Girola-mi A, Thein SL. A common point mutation producing type la antithrombin III deficiency: AT 129 CGA to TGA (Arg to Stop). Thromb Res 1991; 64: 621-625
78 Tomonori A, Iwahana H, Yoshimoto K, Shigekiyo T, Saito S, Itakura M. Two new nonsense mutations in type la antithrombin III deficiency at Leul40 and Argl97. Thromb Haemost 1992; 68: 455-459
79 Jochmans K, Lissens W, Yin T, Michiels JJ, van der Luit L, Peerlinck K, Vervoot R, De Wale M, Liebaers I. Molecular basis for type I antithrombin deficiency: identification of two novel mutations and evidence for a de novo splice mutation. Blood 1994; 84: 3742-3748
80 Perry DJ, Daly ME, Colvin BT, Brown K, Carrell RW. Two antithrombin mutations in a compound heterozygote: Met20Thr and Tyrl66Cys. Am J Hematol 1995; 50: 215-216
81 Berg LP, Grundy CB, Thomas F, Millar DS, Green PJ, Slomski R, Reiss J, Kakkar VV, Cooper DN. De novo splice site mutation in the antithrombin III (AT3) gene causing recurrent venous thrombosis: demonstration of exon skipping by ectopic transcript analysis. Genomics 1992; 13: 1359-1361
82 Perry DJ, Marshall C, Borg JY, Tait RC, Daly ME, Walker ID, Carrell RW. Two new antithrombin variants, Asn 187 Lys, indicate a functional role for asparagine 187. Blood Coagul Fibrinolysis 1995; 06: 51-54
83 Michiels JJ, van der Luit L, van Vliet H, Jochmans K, Lissens W. Nonsense mutation in Arg 197 stop in a Dutch family with type I hereditary antithrombin deficiency causing thrombophilia. Thromb Res 1995; 78: 251-254
84 Vidaud D, Emmerich J, Sirieix ME, Sié P, Alhenc-Gelas M, Aiach M. Molecular basis for antithrombin III type I deficiency: 3 novel mutations located in exon IV. Blood 1991; 78: 2305-2309
85 Grundy CB, Thomas F, Millar DS, Krawczak M, Melissari E, Lindo V, Moffat E, Kakkar VV, Cooper DN. Recurrent deletion in the human antithrombin III gene. Blood 1991; 78: 1027-1032
86 Grundy CB, Holding S, Millar DS, Kakkar VV, Cooper DN. A novel mis-sense mutation in the antithrombin III gene (Ser 349 to Pro) causing recurrent venous thrombosis. Human Genetics 1992; 88: 707-708
87 Emmerich J, Chadeuf G, Alhenc-Gelas M, Gouault-Heilmann M, Toulon P, Fiessinger JN, Aiach M. Molecular basis of antithrombin type I deficiency: the first large in-frame deletion and two novel mutations in exon 6. Thromb Haemost 1994; 72: 534-539
88 White D, Abraham G, Carter C, Kakkar VV, Cooper DN. A novel mis-sense mutation in the antithrombin III gene (Ala 387 to Val) causing recurrent venous thrombosis. Human Genetics 1993; 90: 472-473
89 Jochmans K, Lissens W, Vervoot R, Peeters S, De Wale M, Liebaers I. Antithrombin-Gly 424 Arg: a novel point mutation responsible for type I antithrombin deficiency and neonatal thrombosis. Blood 1994; 83: 146-151
90 Femandez-Rachubinski RA, Rachubinski RA, Blajchman MA. Partial deletion of antithrombin III allele in a kindred with a type I deficiency. Blood 1992; 80: 1476-1485
91 Olds RJ, Lane DA, Chowdury V, Samson D, DeStafano V, Leone G, Wiesel ML, Cazenave JP, Conard J, Thein SL. Major rearrangements within the antithrombin gene locus: an unusual cause for antithrombin deficiency. Brit J Haematol 1992; 40
92 Winter JH, Bennett B, Watt JL, Brown T, San Roman C, Schinzel A, King J, Cooke PJL. Confirmation of linkage between antithrombin III and Duffy blood group and assignment of AT3 to lq22-25. Annals of Human Genetics 1982; 26: 29-34
93 Prochownik EV, Antonarakis S, Bauer KA, Rosenberg RD, Fearon ER, Orkin SH. Molecular heterogeneity of inherited antithrombin III deficiency. N Eng J Med 1983; 308: 1549-1552
94 Bock SC, Prochownik EV. Molecular genetic survey of 16 kindreds with hereditary antithrombin III deficiency. Blood 1987; 70: 1273-1278
95 Devraj-Kizuk R, Chui DHK, Prochownik EV, Carter CJ, Ofosu FA, Blajchman MA. Antithrombin III Hamilton: a gene with a point mutation (guanine to adenine) in codon 382 causing impaired serine protease reactivity. Blood 1988; 72: 1518-1523
96 Austin RC, Rachubinski RA, Ofosu FA, Blajchman MA. Antithrombin-III-Hamilton, Ala 382 to Thr: an antithrombin-III variant that acts as a substrate but not an inhibitor of a-thrombin and Factor Xa. Blood 1991; 77: 2185-2189
97 Perry DJ, Carrell RW. CpG dinucleotides are »hotspots« for mutation in the antithrombin III gene. Twelve variants identified using the polymerase chain reaction. Molecular Biology in Medicine 1989; 06: 239-243
98 Mohlo-Sabatier P, Aiach M, Gaillard I, Fiessinger JN, Fischer AM, Cha-deuf G, Clauser E. Molecular characterization of antithrombin III (AT III) variants using polymerase chain reaction. Identification of the ATIII Charleville as an Ala384 Pro mutation. J Clin Invest 1989; 84: 1236-1241
99 Perry DJ, Harper PL, Fairham S, Daly M, Carrell RW. Antithrombin Cambridge, 384 Ala to Pro: A new variant identified using the polymerase chain reaction. Federation of European Biochemical Societies Letters 1989; 254: 174-176
100 Penwarchuk WJ, Femandez-Rachubinski F, Rachubinski RA, Blajchman MA. Antithrombin III Sudbury, an Ala 384 to Pro mutation with abnormal thrombin binding activity and thrombotic diathesis. Thromb Res 1990; 59: 793-798
101 Perry DJ, Daly M, Harper PL, Tait RC, Price J, Walker ID, Carrell RW. Antithrombin Cambridge II 384 Ala to Ser Further evidence of the role of the reactive centre loop in the inhibitory function of the serpin. Federation of European Biochemical Societies Letters 1991; 285: 248-250
102 Erdjument H, Lane DA, Ireland H, DiMarzo V, Panico M, Morris HR, Tripodi A, Mannucci PM. Antithrombin Milano, single amino acid substitution at the reactive site, Arg 393 to Cys. Thomb Haemost 1988; 60: 471-475
103 Ireland H, Lane DA, Thompson E, Olds R, Thein SL, Hach-Wunderle V, Scharrer I. Antithrombin Frankfurt I: arginine to cysteine substitution at the reactive site and formation of a variant antithrombin-albumin covalent complex. Thromb Haemost 1991; 65: 913
104 Lane DA, Erdjument H, Flynn A, DiMarzo V, Panico M, Morris H, Greaves M, Dolan G, Preston FE. Antithrombin Sheffield: amino acid substitution at the reactive site (Arg 393 to His) causing thrombosis. Brit J Haematol 1989; 71: 91-96
105 Erdjument H, Lane DA, Panico M, DiMarzo V, Morris HR, Bauer K, Rosenberg RD. Antithrombin Chicago, amino acid substitution of arginine 393 to histidine. Thromb Res 1989; 54: 613-619
106 Owen MC, George PM, Lane DA, Boswell DR. PI variant antithrombins Glasgow (393 Arg to His) and Pescara (393 Arg to Pro) have increased heparin affinity and are resistant to catalytic cleavage by elastase Implications for the heparin activation mechanism. Federation of European Biochemical Societies Letters 1991; 280: 216-220
107 Olds RJ, Lane D, Caso R, Tripodi A, Mannucci PM, Thein SL. Antithrombin III Milano 2: a single base substitution in the thrombin binding domain detected with PCR and direct genomic sequencing. Nucleic Acids Research 1989; 17: 10511
108 Chang JY, Tran TH. Antithrombin Basel Identification of a Pro-Leu substitution in a hereditary abnormal antithrombin with impaired heparin cofactor activity. J Biol Chemistry 1986; 261: 1174-1176
109 Daly M, Bruce D, Perry DJ, Price J, Harper PL, O’Meara A, Carrell RW. Antithrombin Dublin (-3 Val to Glu): an N-terminal variant which has an aberrant signal peptide cleavage site. Federation of European Biochemical Societies Letters 1990; 273: 87-90
110 Chowdhury V, Mille B, Olds RJ, Lane DA, Watton J, Barrowcliffe TW, Pabinger I, Woodcock BE, Thein SL. Antithrombins Southport (99 Leu to Val) and Vienna (118 Gin to Pro): two novel antithrombin variants with abnormal heparin binding. Brit J Haematol 1995; 89: 602-609
111 Duchange N, Chasse JF, Cohen GN, Zakin MM. Identification of a mutation leading to cysteine replacement in a silent deficiency. Nucleic Acids Research 1986; 14: 2408
112 Brunei F, Duchange N, Fischer AM, Cohen GN, Zakin MM. Antithrombin III Alger: a new case of Arg 47-Cys mutation. Am J Haematol 1987; 25: 223-224
113 Olds RJ, Lane DA, Caso R, Girolami A, Thein SL. Antithrombin III Padua II: a single base substitution in exon 2 detected using PCR and direct genomic sequencing. Nucleic Acids Research 1990; 18: 1926
114 Owen MC, Shaw GJ, Grau E, Fontcuberta J, Carrell RW, Boswell DR. Molecular characterisation of antithrombin Barcelona 2: 47 arginine to cysteine. Thromb Res 1989; 55: 451-457
115 Femandez-Rachubinski F, Rachubinski R, Blajchman MA. Genetic characterisation of kindreds with antithrombin III (AT-III) deficiency using selected amplification of the gene. Blood 1990; 76: 506a
116 Ueyama H, Murakami T, Nishiguchi S, Maeda S, Hashimoto Y, Okajima K, Shimada K, Araki S. Antithrombin Kumamoto Identification of a point mutation and genotype analysis of the family. Thromb Haemost 1990; 63: 231-234
117 Borg JY, Owen MC, Soria C, Soria J, Caen J, Carrell RW. Arginine 47 is a prime heparin binding site in antithrombin. A new variant Rouen II 47 Arg to Ser. Journal of Clinical Investigation 1988; 81: 1292-1296
118 Owen MC, Borg JY, Soria C, Soria J, Caen J, Carrell RW. Heparin binding defect in new antithrombin III variant: Rouen, 47 Arg to His. Blood 1987; 69: 1275-1279
119 Caso R, Lane DA, Thompson E, Zangouras D, Panico M, Morris H, Olds RJ, Thein SL, Girolami A. Antithrombin Padua I: impaired heparin binding caused by an Arg 47 to His (CGT to CAT) substitution. Thromb Res 1990; 58: 185-190
120 Wolf M, Boyer-Neumann C, Mohlo-Sabatier P, Neumann C, Meyer D, Larrieu MJ. Familial variant of antithrombin III (AT III Bligny, 47 Arg to His) associated with protein C deficiency. Thromb Haemost 1990; 63: 215-219
121 Olds RJ, Lane DA, Boisclair M, Sas G, Bock SC, Thein SL. Antithrombin Budapest 3 an antithrombin variant with reduced heparin affinity resulting from the substitution L99F. Federation of European Societies Letters 1992; 300: 241-246
122 Okajima K, Abe H, Maeda S, Motomura M, Tsujihata M, Nagataki S, Okabe H, Takatsuki K. Antithrombin III Nagasaki (Seri 16-Pro): a heterozygous variant with defective heparin binding associated with thrombosis. Blood 1993; 81: 1300-1305
123 Olds RJ, Thein SL, Ireland H, Lane DA, Boisclair M, Conard J, Horellou MH. Identification of 402 phenylalanine as a functionally important residue in antithrombin. Thromb Haemost 1991; 65: 670
124 Emmerich J, Chadeuf G, Coetzee MJ, Alhenc-Gelas M, Friessinger J-N, Aiach M. A phenylalanine 402 to leucine mutation is responsible for a stable inactive conformation of antithrombin. Thromb Res 1994; 76: 307-315
125 Bock SC, Silberman JA, Wikoff W, Abildgaard U, Hultin MB. Identification of a threonine for alanine substitution at residue 404 of antithrombin III Oslo suggests integrity of the 404-407 region is important for maintaining normal inhibitor levels. Thromb Haemost 1989; 62: 494
126 Nakagawa M, Tanaka S, Tsuji H, Takada O, Ono T. Congenital antithrombin deficiency (ATIII Kyoto): identification of a point mutation altering arginine-406 to methionine behind the reactive site. Thromb Res 1991; 64: 101-108
127 Olds RJ, Lane DA, Caso R, Panico M, Morris HR, Sas G, Dawes J, Thein SL. Antithrombin III Budapest: a single amino acid substitution (429Pro to Leu) in a region highly conserved in the serpin super family. Blood 1992; 79: 1206-1212
128 Bock SC, Levitan DJ. Characterisation of an unusual length polymorphism 5’ to the antithrombin III gene. Nucleic Acids Research 1983; 11: 8569-8582
129 Bock SC, Radziejewska E. A Nhe 1 RFLP in the human antithrombin III gene (lq23-25) (AT3). Nucleic Acids Research 1991; 19: 2519
130 Daly ME, Perry DJ. Dde I polymorphism in intron 5 in the antithrombin III gene. Nucleic Acids Research 1990; 18: 5583
131 Wu S, Seino S, Bell GI. Human antithrombin III (AT3) gene length polymorphism revealed by the polymerase chain reaction. Nucleic Acids Research 1989; 17: 6433