| Structural highlights
Disease
FA8_HUMAN Defects in F8 are the cause of hemophilia A (HEMA) [MIM:306700. A disorder of blood coagulation characterized by a permanent tendency to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery. Note=Of particular interest for the understanding of the function of F8 is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8 in their plasma (at least 30% of normal), but the protein is non-functional; i.e. the F8 activity is much less than the plasma protein level. CRM-reduced is another category of patients in which the F8C antigen and activity are reduced to approximately the same level. Most mutations are CRM negative, and probably affect the folding and stability of the protein.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] [77] [78]
Function
FA8_HUMAN Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.FA8_PIG Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
Publication Abstract from PubMed
BACKGROUND: Hemophilia A arises from dysfunctional or deficient coagulation factor (F)VIII and leads to inefficient fibrin clot formation and uncontrolled bleeding events. The development of antibody inhibitors is a clinical complication in hemophilia A patients receiving FVIII replacement therapy. LE2E9 is an anti-C1 domain inhibitor previously isolated from a mild/moderate hemophilia A patient and disrupts FVIII interactions with von Willebrand factor and FIXa, though the intermolecular contacts that underpin LE2E9-mediated FVIII neutralization are undefined. OBJECTIVES: To determine the structure of the complex between FVIII and LE2E9 and characterize its mechanism of inhibition. METHODS: FVIII was bound to the antigen binding fragment (Fab) of NB2E9, a recombinant construct of LE2E9, and its structure was determined by cryogenic electron microscopy. RESULTS: This report communicates the 3.46 A structure of FVIII bound to NB2E9, with its epitope comprising FVIII residues S2040 to Y2043, K2065 to W2070, and R2150 to H2155. Structural analysis reveals that the LE2E9 epitope overlaps with portions of the epitope for 2A9, a murine-derived inhibitor, suggesting that these residues represent a shared antigenic region on the C1 domain between FVIII(-/-) mice and hemophilia A patients. Furthermore, the FVIII:NB2E9 structure elucidates the orientation of the LE2E9 glycan, illustrating how the glycan sterically blocks interactions between the FVIII C1 domain and the von Willebrand factor D' domain. A putative model of the FVIIIa:FIXa complex suggests potential clashing between the NB2E9 glycan and FIXa light chain. CONCLUSION: These results describe an antigenic "hotspot" on the FVIII C1 domain and provide a structural basis for engineering FVIII replacement therapeutics with reduced antigenicity.
, PMID:38849084[79]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gitschier J, Wood WI, Shuman MA, Lawn RM. Identification of a missense mutation in the factor VIII gene of a mild hemophiliac. Science. 1986 Jun 13;232(4756):1415-6. PMID:3012775
- ↑ Levinson B, Janco R, Phillips J 3rd, Gitschier J. A novel missense mutation in the factor VIII gene identified by analysis of amplified hemophilia DNA sequences. Nucleic Acids Res. 1987 Dec 10;15(23):9797-805. PMID:3122181
- ↑ Youssoufian H, Antonarakis SE, Bell W, Griffin AM, Kazazian HH Jr. Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides. Am J Hum Genet. 1988 May;42(5):718-25. PMID:2833855
- ↑ Youssoufian H, Wong C, Aronis S, Platokoukis H, Kazazian HH Jr, Antonarakis SE. Moderately severe hemophilia A resulting from Glu----Gly substitution in exon 7 of the factor VIII gene. Am J Hum Genet. 1988 Jun;42(6):867-71. PMID:2835904
- ↑ O'Brien DP, Tuddenham EG. Purification and characterization of factor VIII 1,689-Cys: a nonfunctional cofactor occurring in a patient with severe hemophilia A. Blood. 1989 Jun;73(8):2117-22. PMID:2499363
- ↑ Shima M, Ware J, Yoshioka A, Fukui H, Fulcher CA. An arginine to cysteine amino acid substitution at a critical thrombin cleavage site in a dysfunctional factor VIII molecule. Blood. 1989 Oct;74(5):1612-7. PMID:2506948
- ↑ Chan V, Chan TK, Tong TM, Todd D. A novel missense mutation in exon 4 of the factor VIII:C gene resulting in moderately severe hemophilia A. Blood. 1989 Dec;74(8):2688-91. PMID:2510835
- ↑ Inaba H, Fujimaki M, Kazazian HH Jr, Antonarakis SE. Mild hemophilia A resulting from Arg-to-Leu substitution in exon 26 of the factor VIII gene. Hum Genet. 1989 Mar;81(4):335-8. PMID:2495245
- ↑ Arai M, Inaba H, Higuchi M, Antonarakis SE, Kazazian HH Jr, Fujimaki M, Hoyer LW. Direct characterization of factor VIII in plasma: detection of a mutation altering a thrombin cleavage site (arginine-372----histidine). Proc Natl Acad Sci U S A. 1989 Jun;86(11):4277-81. PMID:2498882
- ↑ Arai M, Higuchi M, Antonarakis SE, Kazazian HH Jr, Phillips JA 3rd, Janco RL, Hoyer LW. Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A. Blood. 1990 Jan 15;75(2):384-9. PMID:2104766
- ↑ Casula L, Murru S, Pecorara M, Ristaldi MS, Restagno G, Mancuso G, Morfini M, De Biasi R, Baudo F, Carbonara A, et al.. Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent. Blood. 1990 Feb 1;75(3):662-70. PMID:2105106
- ↑ Pattinson JK, McVey JH, Boon M, Ajani A, Tuddenham EG. CRM+ haemophilia A due to a missense mutation (372----Cys) at the internal heavy chain thrombin cleavage site. Br J Haematol. 1990 May;75(1):73-7. PMID:1973901
- ↑ Higuchi M, Wong C, Kochhan L, Olek K, Aronis S, Kasper CK, Kazazian HH Jr, Antonarakis SE. Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA. Genomics. 1990 Jan;6(1):65-71. PMID:2105906
- ↑ Traystman MD, Higuchi M, Kasper CK, Antonarakis SE, Kazazian HH Jr. Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene. Genomics. 1990 Feb;6(2):293-301. PMID:2106480
- ↑ Kogan S, Gitschier J. Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2092-6. PMID:2107542
- ↑ Paynton C, Sarkar G, Sommer SS. Identification of mutations in two families with sporadic hemophilia A. Hum Genet. 1991 Aug;87(4):397-400. PMID:1908817
- ↑ Higuchi M, Kazazian HH Jr, Kasch L, Warren TC, McGinniss MJ, Phillips JA 3rd, Kasper C, Janco R, Antonarakis SE. Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7405-9. PMID:1908096
- ↑ Schwaab R, Ludwig M, Kochhan L, Oldenburg J, McVey JH, Egli H, Brackmann HH, Olek K. Detection and characterisation of two missense mutations at a cleavage site in the factor VIII light chain. Thromb Res. 1991 Feb 1;61(3):225-34. PMID:1851341
- ↑ Krepelova A, Vorlova Z, Acquila M, Mori P. GAA(Glu)272----AAA(Lys) and CGA(Arg)1941----CAA(Gln) in the factor VIII gene in two haemophilia A patients of Czech origin. Br J Haematol. 1992 Jul;81(3):458. PMID:1356412
- ↑ Economou EP, Kazazian HH Jr, Antonarakis SE. Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP). Genomics. 1992 Jul;13(3):909-11. PMID:1639429
- ↑ Reiner AP, Thompson AR. Screening for nonsense mutations in patients with severe hemophilia A can provide rapid, direct carrier detection. Hum Genet. 1992 Apr;89(1):88-94. PMID:1349567
- ↑ Nafa K, Baudis M, Deburgrave N, Bardin JM, Sultan Y, Kaplan JC, Delpech M. A novel mutation (Arg-->Leu in exon 18) in factor VIII gene responsible for moderate hemophilia A. Hum Mutat. 1992;1(1):77-8. PMID:1301194 doi:https://dx.doi.org/10.1002/humu.1380010114
- ↑ Diamond C, Kogan S, Levinson B, Gitschier J. Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A. Hum Mutat. 1992;1(3):248-57. PMID:1301932 doi:https://dx.doi.org/10.1002/humu.1380010312
- ↑ Jonsdottir S, Diamond C, Levinson B, Magnusson S, Jensson O, Gitschier J. Missense mutations causing mild hemophilia A in Iceland detected by denaturing gradient gel electrophoresis. Hum Mutat. 1992;1(6):506-8. PMID:1301960 doi:https://dx.doi.org/10.1002/humu.1380010610
- ↑ McGinniss MJ, Kazazian HH Jr, Hoyer LW, Bi L, Inaba H, Antonarakis SE. Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A. Genomics. 1993 Feb;15(2):392-8. PMID:8449505 doi:https://dx.doi.org/S0888-7543(83)71073-6
- ↑ Pieneman WC, Reitsma PH, Briet E. Double strand conformation polymorphism (DSCP) detects two point mutations at codon 280 (AAC-->ATC) and at codon 431 (TAC-->AAC) of the blood coagulation factor VIII gene. Thromb Haemost. 1993 May 3;69(5):473-5. PMID:8322269
- ↑ Arruda VR, Pieneman WC, Reitsma PH, Deutz-Terlouw PP, Annichino-Bizzacchi JM, Briet E, Costa FF. Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients. Blood. 1995 Oct 15;86(8):3015-20. PMID:7579394
- ↑ Pieneman WC, Deutz-Terlouw PP, Reitsma PH, Briet E. Screening for mutations in haemophilia A patients by multiplex PCR-SSCP, Southern blotting and RNA analysis: the detection of a genetic abnormality in the factor VIII gene in 30 out of 35 patients. Br J Haematol. 1995 Jun;90(2):442-9. PMID:7794769
- ↑ Bidichandani SI, Lanyon WG, Shiach CR, Lowe GD, Connor JM. Detection of mutations in ectopic factor VIII transcripts from nine haemophilia A patients and the correlation with phenotype. Hum Genet. 1995 May;95(5):531-8. PMID:7759074
- ↑ Becker J, Schwaab R, Moller-Taube A, Schwaab U, Schmidt W, Brackmann HH, Grimm T, Olek K, Oldenburg J. Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies. Am J Hum Genet. 1996 Apr;58(4):657-70. PMID:8644728
- ↑ Chan V, Pang A, Chan TP, Chan VW, Chan TK. Molecular characterization of haemophilia A in southern Chinese. Br J Haematol. 1996 May;93(2):451-6. PMID:8639447
- ↑ Rudzki Z, Duncan EM, Casey GJ, Neumann M, Favaloro EJ, Lloyd JV. Mutations in a subgroup of patients with mild haemophilia A and a familial discrepancy between the one-stage and two-stage factor VIII:C methods. Br J Haematol. 1996 Aug;94(2):400-6. PMID:8759905
- ↑ Mazurier C, Gaucher C, Jorieux S, Parquet-Gernez A. Mutations in the FVIII gene in seven families with mild haemophilia A. Br J Haematol. 1997 Feb;96(2):426-7. PMID:9029040
- ↑ Morichika S, Shima M, Kamisue S, Tanaka I, Imanaka Y, Suzuki H, Shibata H, Pemberton S, Gale K, McVey J, Tuddenham EG, Yoshioka A. Factor VIII gene analysis in Japanese CRM-positive and CRM-reduced haemophilia A patients by single-strand conformation polymorphism. Br J Haematol. 1997 Sep;98(4):901-6. PMID:9326186
- ↑ Tavassoli K, Eigel A, Pollmann H, Horst J. Mutational analysis of ectopic factor VIII transcripts from hemophilia A patients: identification of cryptic splice site, exon skipping and novel point mutations. Hum Genet. 1997 Oct;100(5-6):508-11. PMID:9341862
- ↑ Liu M, Murphy ME, Thompson AR. A domain mutations in 65 haemophilia A families and molecular modelling of dysfunctional factor VIII proteins. Br J Haematol. 1998 Dec;103(4):1051-60. PMID:9886318
- ↑ Maugard C, Tuffery S, Aguilar-Martinez P, Schved JF, Gris JC, Demaille J, Claustres M. Protein truncation test: detection of severe haemophilia a mutation and analysis of factor VIII transcripts. Hum Mutat. 1998;11(1):18-22. PMID:9450898 doi:<18::AID-HUMU3>3.0.CO;2-H 10.1002/(SICI)1098-1004(1998)11:1<18::AID-HUMU3>3.0.CO;2-H
- ↑ Theophilus BD, Enayat MS, Higuchi M, Kazazian HH, Antonarakis SE, Hill FG. Independent occurrence of the novel Arg2163 to His mutation in the factor VIII gene in three unrelated families with haemophila A with different phenotypes. Mutations in brief no. 126. Online. Hum Mutat. 1998;11(4):334. PMID:10215414 doi:<334::AID-HUMU20>3.0.CO;2-# 10.1002/(SICI)1098-1004(1998)11:4<334::AID-HUMU20>3.0.CO;2-#
- ↑ Freson K, Peerlinck K, Aguirre T, Arnout J, Vermylen J, Cassiman JJ, Matthijs G. Fluorescent chemical cleavage of mismatches for efficient screening of the factor VIII gene. Hum Mutat. 1998;11(6):470-9. PMID:9603440 doi:<470::AID-HUMU8>3.0.CO;2-A 10.1002/(SICI)1098-1004(1998)11:6<470::AID-HUMU8>3.0.CO;2-A
- ↑ Tavassoli K, Eigel A, Dworniczak B, Valtseva E, Horst J. Identification of four novel mutations in the factor VIII gene: three missense mutations (E1875G, G2088S, I2185T) and a 2-bp deletion (1780delTC). Hum Mutat. 1998;Suppl 1:S260-2. PMID:9452104
- ↑ Tavassoli K, Eigel A, Wilke K, Pollmann H, Horst J. Molecular diagnostics of 15 hemophilia A patients: characterization of eight novel mutations in the factor VIII gene, two of which result in exon skipping. Hum Mutat. 1998;12(5):301-3. PMID:9792405 doi:<301::AID-HUMU2>3.0.CO;2-G 10.1002/(SICI)1098-1004(1998)12:5<301::AID-HUMU2>3.0.CO;2-G
- ↑ Laprise SL, Mak EK, Killoran KA, Layman LC, Gray MR. Use of denaturing gradient gel blots to screen for point mutations in the factor VIII gene. Hum Mutat. 1998;12(6):393-402. PMID:9829908 doi:<393::AID-HUMU5>3.0.CO;2-A 10.1002/(SICI)1098-1004(1998)12:6<393::AID-HUMU5>3.0.CO;2-A
- ↑ Williams IJ, Abuzenadah A, Winship PR, Preston FE, Dolan G, Wright J, Peake IR, Goodeve AC. Precise carrier diagnosis in families with haemophilia A: use of conformation sensitive gel electrophoresis for mutation screening and polymorphism analysis. Thromb Haemost. 1998 Apr;79(4):723-6. PMID:9569180
- ↑ Hay CR, Ludlam CA, Colvin BT, Hill FG, Preston FE, Wasseem N, Bagnall R, Peake IR, Berntorp E, Mauser Bunschoten EP, Fijnvandraat K, Kasper CK, White G, Santagostino E. Factor VIII inhibitors in mild and moderate-severity haemophilia A. UK Haemophilia Centre Directors Organisation. Thromb Haemost. 1998 Apr;79(4):762-6. PMID:9569189
- ↑ Keeling DM, Sukhu K, Kemball-Cook G, Waseem N, Bagnall R, Lloyd JV. Diagnostic importance of the two-stage factor VIII:C assay demonstrated by a case of mild haemophilia associated with His1954-->Leu substitution in the factor VIII A3 domain. Br J Haematol. 1999 Jun;105(4):1123-6. PMID:10554831
- ↑ Strmecki L, Benedik-Dolnicar M, Vouk K, Komel R. Screen of 55 Slovenian haemophilia A patients: identification of 2 novel mutations (S-1R and IVS23+1G-->A) and discussion of mutation spectrum. Mutation in brief no. 241. Online. Hum Mutat. 1999;13(5):413. PMID:10338101 doi:<413::AID-HUMU14>3.0.CO;2-H 10.1002/(SICI)1098-1004(1999)13:5<413::AID-HUMU14>3.0.CO;2-H
- ↑ Moller-Morlang K, Tavassoli K, Eigel A, Pollmann H, Horst J. Mutational-screening in the factor VIII gene resulting in the identification of three novel mutations, one of which is a donor splice mutation. Mutations in brief no. 245. Online. Hum Mutat. 1999;13(6):504. PMID:10408784 doi:<504::AID-HUMU14>3.0.CO;2-9 10.1002/(SICI)1098-1004(1999)13:6<504::AID-HUMU14>3.0.CO;2-9
- ↑ Waseem NH, Bagnall R, Green PM, Giannelli F. Start of UK confidential haemophilia A database: analysis of 142 patients by solid phase fluorescent chemical cleavage of mismatch. Haemophilia Centres. Thromb Haemost. 1999 Jun;81(6):900-5. PMID:10404764
- ↑ Jacquemin M, Lavend'homme R, Benhida A, Vanzieleghem B, d'Oiron R, Lavergne JM, Brackmann HH, Schwaab R, VandenDriessche T, Chuah MK, Hoylaerts M, Gilles JG, Peerlinck K, Vermylen J, Saint-Remy JM. A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor. Blood. 2000 Aug 1;96(3):958-65. PMID:10910910
- ↑ Liu ML, Shen BW, Nakaya S, Pratt KP, Fujikawa K, Davie EW, Stoddard BL, Thompson AR. Hemophilic factor VIII C1- and C2-domain missense mutations and their modeling to the 1.5-angstrom human C2-domain crystal structure. Blood. 2000 Aug 1;96(3):979-87. PMID:10910913
- ↑ Roelse JC, De Laaf RT, Timmermans SM, Peters M, Van Mourik JA, Voorberg J. Intracellular accumulation of factor VIII induced by missense mutations Arg593-->Cys and Asn618-->Ser explains cross-reacting material-reduced haemophilia A. Br J Haematol. 2000 Feb;108(2):241-6. PMID:10691849
- ↑ Schwaab R, Oldenburg J, Kemball-Cook G, Albert T, Juhler C, Hanfland P, Ingerslev J. Assay discrepancy in mild haemophilia A due to a factor VIII missense mutation (Asn694Ile) in a large Danish family. Br J Haematol. 2000 Jun;109(3):523-8. PMID:10886198
- ↑ Tagariello G, Belvini D, Salviato R, Are A, De Biasi E, Goodeve A, Davoli P. Experience of a single Italian center in genetic counseling for hemophilia: from linkage analysis to molecular diagnosis. Haematologica. 2000 May;85(5):525-9. PMID:10800171
- ↑ Goodeve AC, Williams I, Bray GL, Peake IR. Relationship between factor VIII mutation type and inhibitor development in a cohort of previously untreated patients treated with recombinant factor VIII (Recombinate). Recombinate PUP Study Group. Thromb Haemost. 2000 Jun;83(6):844-8. PMID:10896236
- ↑ Akkarapatumwong V, Oranwiroon S, Pung-amritt P, Treesucon A, Thanootarakul P, Veerakul G, Mahasandana C, Panyim S, Yenchitsomanus P. Mutations of the factor VIII gene in thai hemophilia A patients. Hum Mutat. 2000 Jan;15(1):117-8. PMID:10612839 doi:<117::AID-HUMU27>3.0.CO;2-E 10.1002/(SICI)1098-1004(200001)15:1<117::AID-HUMU27>3.0.CO;2-E
- ↑ Leuer M, Oldenburg J, Lavergne JM, Ludwig M, Fregin A, Eigel A, Ljung R, Goodeve A, Peake I, Olek K. Somatic mosaicism in hemophilia A: a fairly common event. Am J Hum Genet. 2001 Jul;69(1):75-87. Epub 2001 Jun 14. PMID:11410838 doi:S0002-9297(07)61447-5
- ↑ Ivaskevicius V, Jurgutis R, Rost S, Muller A, Schmitt C, Wulff K, Herrmann FH, Muller CR, Schwaab R, Oldenburg J. Lithuanian haemophilia A and B registry comprising phenotypic and genotypic data. Br J Haematol. 2001 Mar;112(4):1062-70. PMID:11298607
- ↑ Theophilus BD, Enayat MS, Williams MD, Hill FG. Site and type of mutations in the factor VIII gene in patients and carriers of haemophilia A. Haemophilia. 2001 Jul;7(4):381-91. PMID:11442643
- ↑ Bauduer F, Ducout L, Bendriss P, Falaises B, Lavergne JM. Mild haemophilia A discovered in a previously multi-operated 73-year-old man: characterization of a new mutation. Haemophilia. 2001 Jul;7(4):419-21. PMID:11442647
- ↑ Timur AA, Gurgey A, Aktuglu G, Kavakli K, Canatan D, Olek K, Caglayan SH. Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations. Haemophilia. 2001 Sep;7(5):475-81. PMID:11554935
- ↑ Bogdanova N, Lemcke B, Markoff A, Pollmann H, Dworniczak B, Eigel A, Horst J. Seven novel and four recurrent point mutations in the factor VIII (F8C) gene. Hum Mutat. 2001 Dec;18(6):546. PMID:11748850 doi:10.1002/humu.1234
- ↑ Vidal F, Farssac E, Altisent C, Puig L, Gallardo D. Rapid hemophilia A molecular diagnosis by a simple DNA sequencing procedure: identification of 14 novel mutations. Thromb Haemost. 2001 Apr;85(4):580-3. PMID:11341489
- ↑ Valleix S, Vinciguerra C, Lavergne JM, Leuer M, Delpech M, Negrier C. Skewed X-chromosome inactivation in monochorionic diamniotic twin sisters results in severe and mild hemophilia A. Blood. 2002 Oct 15;100(8):3034-6. PMID:12351418 doi:10.1182/blood-2002-01-0277
- ↑ Mazurier C, Parquet-Gernez A, Gaucher C, Lavergne JM, Goudemand J. Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A. Br J Haematol. 2002 Nov;119(2):390-2. PMID:12406074
- ↑ Sukarova-Stefanovska E, Zisovski N, Muratovska O, Kostova S, Efremov GD. Three novel point mutations causing haemophilia A. Haemophilia. 2002 Sep;8(5):715-8. PMID:12199686
- ↑ Cutler JA, Mitchell MJ, Smith MP, Savidge GF. The identification and classification of 41 novel mutations in the factor VIII gene (F8C). Hum Mutat. 2002 Mar;19(3):274-8. PMID:11857744 doi:10.1002/humu.10056
- ↑ Frusconi S, Passerini I, Girolami F, Masieri M, Linari S, Longo G, Morfini M, Torricelli F. Identification of seven novel mutations of F8C by DHPLC. Hum Mutat. 2002 Sep;20(3):231-2. PMID:12203998 doi:10.1002/humu.9052
- ↑ Citron M, Godmilow L, Ganguly T, Ganguly A. High throughput mutation screening of the factor VIII gene (F8C) in hemophilia A: 37 novel mutations and genotype-phenotype correlation. Hum Mutat. 2002 Oct;20(4):267-74. PMID:12325022 doi:10.1002/humu.10119
- ↑ Liu ML, Nakaya S, Thompson AR. Non-inversion factor VIII mutations in 80 hemophilia A families including 24 with alloimmune responses. Thromb Haemost. 2002 Feb;87(2):273-6. PMID:11858487
- ↑ Klopp N, Oldenburg J, Uen C, Schneppenheim R, Graw J. 11 hemophilia A patients without mutations in the factor VIII encoding gene. Thromb Haemost. 2002 Aug;88(2):357-60. PMID:12195713
- ↑ Bicocchi MP, Pasino M, Lanza T, Bottini F, Boeri E, Mori PG, Molinari AC, Rosano C, Acquila M. Analysis of 18 novel mutations in the factor VIII gene. Br J Haematol. 2003 Sep;122(5):810-7. PMID:12930394
- ↑ Habart D, Kalabova D, Novotny M, Vorlova Z. Thirty-four novel mutations detected in factor VIII gene by multiplex CSGE: modeling of 13 novel amino acid substitutions. J Thromb Haemost. 2003 Apr;1(4):773-81. PMID:12871415
- ↑ Yenchitsomanus P, Akkarapatumwong V, Pung-Amritt P, Intorasoot S, Thanootarakul P, Oranwiroon S, Veerakul G, Mahasandana C. Genotype and phenotype of haemophilia A in Thai patients. Haemophilia. 2003 Mar;9(2):179-86. PMID:12614369
- ↑ Bicocchi MP, Pasino M, Lanza T, Bottini F, Molinari AC, Caprino D, Rosano C, Acquila M. Small FVIII gene rearrangements in 18 hemophilia A patients: five novel mutations. Am J Hematol. 2005 Feb;78(2):117-22. PMID:15682412 doi:10.1002/ajh.20234
- ↑ Hill M, Deam S, Gordon B, Dolan G. Mutation analysis in 51 patients with haemophilia A: report of 10 novel mutations and correlations between genotype and clinical phenotype. Haemophilia. 2005 Mar;11(2):133-41. PMID:15810915 doi:10.1111/j.1365-2516.2005.01069.x
- ↑ Cai XH, Wang XF, Dai J, Fang Y, Ding QL, Xie F, Wang HL. Female hemophilia A heterozygous for a de novo frameshift and a novel missense mutation of factor VIII. J Thromb Haemost. 2006 Sep;4(9):1969-74. Epub 2006 Jun 27. PMID:16805874 doi:JTH2105
- ↑ Vencesla A, Corral-Rodriguez MA, Baena M, Cornet M, Domenech M, Baiget M, Fuentes-Prior P, Tizzano EF. Identification of 31 novel mutations in the F8 gene in Spanish hemophilia A patients: structural analysis of 20 missense mutations suggests new intermolecular binding sites. Blood. 2008 Apr 1;111(7):3468-78. doi: 10.1182/blood-2007-08-108068. Epub 2008, Jan 9. PMID:18184865 doi:10.1182/blood-2007-08-108068
- ↑ Albanez S, Ruiz-Saez A, Boadas A, de Bosch N, Porco A. Identification of factor VIII gene mutations in patients with severe haemophilia A in Venezuela: identification of seven novel mutations. Haemophilia. 2011 Sep;17(5):e913-8. doi: 10.1111/j.1365-2516.2011.02500.x. Epub, 2011 Mar 4. PMID:21371196 doi:10.1111/j.1365-2516.2011.02500.x
- ↑ Childers KC, Cowper B, Vaughan JD, McGill JR, Davulcu O, Lollar P, Doering CB, Coxon CH, Spiegel PC Jr. Structural basis for inhibition of coagulation factor VIII reveals a shared antigenic hotspot on the C1 domain. J Thromb Haemost. 2024 Sep;22(9):2449-2459. PMID:38849084 doi:10.1016/j.jtha.2024.05.024
|
