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Semin Thromb Hemost 2013; 39(06): 632-641
DOI: 10.1055/s-0033-1353392
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Factor XIII Deficiency: An Update

Verena Schroeder
1   University Clinic of Hematology, Hemostasis Research Laboratory, University Hospital, University of Bern, Bern, Switzerland
,
Hans P. Kohler
1   University Clinic of Hematology, Hemostasis Research Laboratory, University Hospital, University of Bern, Bern, Switzerland
2   Department of Internal Medicine, Spital Netz Bern Hospitals, Bern, Switzerland
› Author Affiliations
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Publication History

Publication Date:
08 August 2013 (online)

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Abstract

Confirmation of suspected congenital factor XIII (FXIII) deficiency still represents a diagnostic challenge in the field of rare bleeding disorders. Because of the lack of awareness and difficulties associated with timing of blood sampling, FXIII laboratory assays, and interpretation of laboratory results, diagnoses of FXIII deficiency are still missed all over the world with potentially fatal consequences from severe bleeding complications. Better knowledge of FXIII biochemical properties and function and understanding of the principles and limitations of FXIII laboratory assays can prevent missed diagnoses, and patients will benefit from better care. This review gives a detailed overview and update about congenital FXIII deficiency, its epidemiology, and molecular genetics. It highlights the importance of newer specific FXIII assays and their principles to avoid any missed diagnosis of FXIII deficiency. This review also gives an update on the therapeutic options for patients suffering from this rare but life-threatening disease.

Keywords

factor XIII - rare bleeding disorders - congenital FXIII deficiency - transglutaminase
 

  • References

  • 1 Perez DL, Diamond EL, Castro CM , et al. Factor XIII deficiency related recurrent spontaneous intracerebral hemorrhage: a case and literature review. Clin Neurol Neurosurg 2011; 113 (2) 142-145
    CrossrefPubMedGoogle Scholar
  • 2 Karimi M, Bereczky Z, Cohan N, Muszbek L. Factor XIII deficiency. Semin Thromb Hemost 2009; 35 (4) 426-438
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Muszbek L, Bereczky Z, Bagoly Z, Komáromi I, Katona E. Factor XIII: a coagulation factor with multiple plasmatic and cellular functions. Physiol Rev 2011; 91 (3) 931-972
    CrossrefPubMedGoogle Scholar
  • 4 Lord ST. Molecular mechanisms affecting fibrin structure and stability. Arterioscler Thromb Vasc Biol 2011; 31 (3) 494-499
    CrossrefPubMedGoogle Scholar
  • 5 Fraser SR, Booth NA, Mutch NJ. The antifibrinolytic function of factor XIII is exclusively expressed through α2-antiplasmin cross-linking. Blood 2011; 117 (23) 6371-6374
    CrossrefPubMedGoogle Scholar
  • 6 Inbal A, Lubetsky A, Krapp T , et al. Impaired wound healing in factor XIII deficient mice. Thromb Haemost 2005; 94 (2) 432-437
    PubMedGoogle Scholar
  • 7 Dardik R, Loscalzo J, Inbal A. Factor XIII (FXIII) and angiogenesis. J Thromb Haemost 2006; 4 (1) 19-25
    CrossrefPubMedGoogle Scholar
  • 8 Ichinose A, Asahina T, Kobayashi T. Congenital blood coagulation factor XIII deficiency and perinatal management. Curr Drug Targets 2005; 6 (5) 541-549
    CrossrefPubMedGoogle Scholar
  • 9 Schroeder V, Kohler HP. New developments in the area of factor XIII. J Thromb Haemost 2013; 11 (2) 234-244
    CrossrefPubMedGoogle Scholar
  • 10 Anwar R, Minford A, Gallivan L, Trinh CH, Markham AF. Delayed umbilical bleeding—a presenting feature for factor XIII deficiency: clinical features, genetics, and management. Pediatrics 2002; 109 (2) E32
    CrossrefPubMedGoogle Scholar
  • 11 Duckert F, Jung E, Shmerling DH. A hitherto undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency. Thromb Diath Haemorrh 1960; 5: 179-186
    PubMedGoogle Scholar
  • 12 Laki K, Lóránd L. On the solubility of fibrin clots. Science 1948; 108 (2802) 280
    CrossrefPubMedGoogle Scholar
  • 13 Schroeder V, Meili E, Cung T, Schmutz P, Kohler HP. Characterisation of six novel A-subunit mutations leading to congenital factor XIII deficiency and molecular analysis of the first diagnosed patient with this rare bleeding disorder. Thromb Haemost 2006; 95 (1) 77-84
    PubMedGoogle Scholar
  • 14 Anwar R, Miloszewski KJ. Factor XIII deficiency. Br J Haematol 1999; 107 (3) 468-484
    CrossrefPubMedGoogle Scholar
  • 15 Board PG, Losowsky MS, Miloszewski KJ. Factor XIII: inherited and acquired deficiency. Blood Rev 1993; 7 (4) 229-242
    CrossrefPubMedGoogle Scholar
  • 16 Muszbek L, Bagoly Z, Cairo A, Peyvandi F. Novel aspects of factor XIII deficiency. Curr Opin Hematol 2011; 18 (5) 366-372
    CrossrefPubMedGoogle Scholar
  • 17 Peyvandi F, Duga S, Akhavan S, Mannucci PM. Rare coagulation deficiencies. Haemophilia 2002; 8 (3) 308-321
    CrossrefPubMedGoogle Scholar
  • 18 Biswas A, Ivaskevicius V, Seitz R, Thomas A, Oldenburg J. An update of the mutation profile of Factor 13 A and B genes. Blood Rev 2011; 25 (5) 193-204
    CrossrefPubMedGoogle Scholar
  • 19 Hashiguchi T, Saito M, Morishita E, Matsuda T, Ichinose A. Two genetic defects in a patient with complete deficiency of the b-subunit for coagulation factor XIII. Blood 1993; 82 (1) 145-150
    PubMedGoogle Scholar
  • 20 Koseki S, Souri M, Koga S , et al. Truncated mutant B subunit for factor XIII causes its deficiency due to impaired intracellular transportation. Blood 2001; 97 (9) 2667-2672
    CrossrefPubMedGoogle Scholar
  • 21 Izumi T, Hashiguchi T, Castaman G , et al. Type I factor XIII deficiency is caused by a genetic defect of its b subunit: insertion of triplet AAC in exon III leads to premature termination in the second Sushi domain. Blood 1996; 87 (7) 2769-2774
    PubMedGoogle Scholar
  • 22 Souri M, Izumi T, Higashi Y, Girolami A, Ichinose A. A founder effect is proposed for factor XIII B subunit deficiency caused by the insertion of triplet AAC in exon III encoding the second Sushi domain. Thromb Haemost 1998; 80 (2) 211-213
    PubMedGoogle Scholar
  • 23 Ivaskevicius V, Biswas A, Loreth R , et al. Mutations affecting disulphide bonds contribute to a fairly common prevalence of F13B gene defects: results of a genetic study in 14 families with factor XIII B deficiency. Haemophilia 2010; 16 (4) 675-682
    PubMedGoogle Scholar
  • 24 Ivaskevicius V, Seitz R, Kohler HP , et al; Study Group. International registry on factor XIII deficiency: a basis formed mostly on European data. Thromb Haemost 2007; 97 (6) 914-921
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Kohler HP, Ichinose A, Seitz R, Ariens RAS, Muszbek L. Factor XIII and Fibrinogen SSC Subcommittee of the ISTH. Diagnosis and classification of factor XIII deficiencies. J Thromb Haemost 2011; 9 (7) 1404-1406
    CrossrefPubMedGoogle Scholar
  • 26 Ivaskevicius V, Biswas A, Thomas A , et al. Identification of two novel missense mutations in F13A gene affecting thrombin cleavage site (Arg37) of factor XIII A-subunit. Hamostaseologie 2012; 32 (1) A2-A107 [abstract ED20–5, A22]
    PubMedGoogle Scholar
  • 27 Egbring R, Seitz R, Gürten GV, Köther M, Barthels M, Fuchs G. Bleeding complications in heterozygotes with congenital factor XIII deficiency. In: Mosesson MW, ed. Fibrinogen—Biochemistry, Biological Functions, Gene Regulation and Expression. Amsterdam: Elsevier; 1988: 341-346
    Google Scholar
  • 28 Seitz R, Duckert F, Lopaciuk S, Muszbek L, Rodeghiero F, Seligsohn U. Study Group. ETRO Working Party on Factor XIII questionnaire on congenital factor XIII deficiency in Europe: status and perspectives. Semin Thromb Hemost 1996; 22 (5) 415-418
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Mahmoodi M, Peyvandi F, Afrasiabi A, Ghaffarpasand F, Karimi M. Bleeding symptoms in heterozygous carriers of inherited coagulation disorders in southern Iran. Blood Coagul Fibrinolysis 2011; 22 (5) 396-401
    CrossrefPubMedGoogle Scholar
  • 30 Bolton-Maggs PH, Favaloro EJ, Hillarp A, Jennings I, Kohler HP. Difficulties and pitfalls in the laboratory diagnosis of bleeding disorders. Haemophilia 2012; 18 (Suppl. 04) 66-72
    CrossrefPubMedGoogle Scholar
  • 31 Kárpáti L, Penke B, Katona E, Balogh I, Vámosi G, Muszbek L. A modified, optimized kinetic photometric assay for the determination of blood coagulation factor XIII activity in plasma. Clin Chem 2000; 46 (12) 1946-1955
    PubMedGoogle Scholar
  • 32 Wilmer M, Rudin K, Kolde H , et al. Evaluation of a sensitive colorimetric FXIII incorporation assay. Effects of FXIII Val34Leu, plasma fibrinogen concentration and congenital FXIII deficiency. Thromb Res 2001; 102 (1) 81-91
    CrossrefPubMedGoogle Scholar
  • 33 Ajzner E, Muszbek L. Kinetic spectrophotometric factor XIII activity assays: the subtraction of plasma blank is not omissible [corrected]. J Thromb Haemost 2004; 2 (11) 2075-2077
    CrossrefPubMedGoogle Scholar
  • 34 Ichinose A. Hemorrhagic acquired factor XIII (13) deficiency and acquired hemorrhaphilia 13 revisited. Semin Thromb Hemost 2011; 37 (4) 382-388
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Gerlach R, Tölle F, Raabe A, Zimmermann M, Siegemund A, Seifert V. Increased risk for postoperative hemorrhage after intracranial surgery in patients with decreased factor XIII activity: implications of a prospective study. Stroke 2002; 33 (6) 1618-1623
    CrossrefPubMedGoogle Scholar
  • 36 Kucher N, Schroeder V, Kohler HP. Role of blood coagulation factor XIII in patients with acute pulmonary embolism. Correlation of factor XIII antigen levels with pulmonary occlusion rate, fibrinogen, D-dimer, and clot firmness. Thromb Haemost 2003; 90 (3) 434-438
    PubMedGoogle Scholar
  • 37 Kohler HP, Ariëns RAS, Catto AJ , et al. Factor XIII A-subunit concentration predicts outcome in stroke subjects and vascular outcome in healthy, middle-aged men. Br J Haematol 2002; 118 (3) 825-832
    CrossrefPubMedGoogle Scholar
  • 38 Seitz R, Leugner F, Katschinski M , et al. Ulcerative colitis and Crohn's disease: factor XIII, inflammation and haemostasis. Digestion 1994; 55 (6) 361-367
    CrossrefPubMedGoogle Scholar
  • 39 Zeerleder S, Schroeder V, Lämmle B, Wuillemin WA, Hack CE, Kohler HP. Factor XIII in severe sepsis and septic shock. Thromb Res 2007; 119 (3) 311-318
    CrossrefPubMedGoogle Scholar
  • 40 Matsuoka M, Majima T, Onodera T , et al. Hemorrhagic-acquired factor XIII deficiency associated with tocilizumab for treatment of rheumatoid arthritis. Int J Hematol 2012; 96 (6) 781-785
    CrossrefPubMedGoogle Scholar
  • 41 Lorand L, Maldonado N, Fradera J, Atencio AC, Robertson B, Urayama T. Haemorrhagic syndrome of autoimmune origin with a specific inhibitor against fibrin stabilizing factor (factor XIII). Br J Haematol 1972; 23 (1) 17-27
    PubMedGoogle Scholar
  • 42 Lorand L, Velasco PT, Rinne JR, Amare M, Miller LK, Zucker ML. Autoimmune antibody (IgG Kansas) against the fibrin stabilizing factor (factor XIII) system. Proc Natl Acad Sci U S A 1988; 85 (1) 232-236
    CrossrefPubMedGoogle Scholar
  • 43 Fukue H, Anderson K, McPhedran P, Clyne L, McDonagh J. A unique factor XIII inhibitor to a fibrin-binding site on factor XIIIA. Blood 1992; 79 (1) 65-74
    PubMedGoogle Scholar
  • 44 Hayashi T, Kadohira Y, Morishita E, Asakura H, Souri M, Ichinose A. A case of acquired FXIII deficiency with severe bleeding symptoms. Haemophilia 2012; 18 (4) 618-620
    CrossrefPubMedGoogle Scholar
  • 45 Sugiyama H, Uesugi H, Suzuki S, Tanaka K, Souri M, Ichinose A. Aggressive fatal case of autoimmune hemorrhaphilia resulting from anti-Factor XIII antibodies. Blood Coagul Fibrinolysis 2013; 24 (1) 85-89
    CrossrefPubMedGoogle Scholar
  • 46 Ajzner E, Schlammadinger A, Kerényi A , et al. Severe bleeding complications caused by an autoantibody against the B subunit of plasma factor XIII: a novel form of acquired factor XIII deficiency. Blood 2009; 113 (3) 723-725
    CrossrefPubMedGoogle Scholar
  • 47 Boehlen F, Casini A, Chizzolini C , et al. Acquired factor XIII deficiency: a therapeutic challenge. Thromb Haemost 2013; 109 (3) 479-487
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Nugent DJ. Prophylaxis in rare coagulation disorders—factor XIII deficiency. Thromb Res 2006; 118 (Suppl. 01) S23-S28
    CrossrefPubMedGoogle Scholar
  • 49 Inbal A, Oldenburg J, Carcao M, Rosholm A, Tehranchi R, Nugent D. Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency. Blood 2012; 119 (22) 5111-5117
    CrossrefPubMedGoogle Scholar
  • 50 Kohler HP. Novel treatment for congenital FXIII deficiency. Blood 2012; 119 (22) 5060-5061
    CrossrefPubMedGoogle Scholar
  • 51 Coggan M, Baker R, Miloszewski K, Woodfield G, Board P. Mutations causing coagulation factor XIII subunit A deficiency: characterization of the mutant proteins after expression in yeast. Blood 1995; 85 (9) 2455-2460
    PubMedGoogle Scholar
  • 52 Peyvandi F, Tagliabue L, Menegatti M , et al. Phenotype-genotype characterization of 10 families with severe a subunit factor XIII deficiency. Hum Mutat 2004; 23 (1) 98
    PubMedGoogle Scholar
  • 53 Halverstadt A, Walsh S, Roth SM, Ferrell RE, Hagberg JM. Identification of a novel mutation combination in factor XIII deficiency: genetic update to the first reported case in the United States. Int J Hematol 2006; 83 (2) 144-146
    CrossrefPubMedGoogle Scholar
  • 54 Ivaskevicius V, Biswas A, Bevans C , et al. Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function. Haematologica 2010; 95 (6) 956-962
    CrossrefPubMedGoogle Scholar
  • 55 Castaman G, Giacomelli SH, Ivaskevicius V , et al. Molecular characterization of five Italian families with inherited severe factor XIII deficiency. Haemophilia 2008; 14 (1) 96-102
    PubMedGoogle Scholar
  • 56 Trinh CH, Sh Elsayed W, Eshghi P , et al. Molecular analysis of sixteen unrelated factor XIIIA deficient families from south-east of Iran. Br J Haematol 2008; 140 (5) 581-584
    CrossrefPubMedGoogle Scholar
  • 57 Vysokovsky A, Saxena R, Landau M , et al. Seven novel mutations in the factor XIII A-subunit gene causing hereditary factor XIII deficiency in 10 unrelated families. J Thromb Haemost 2004; 2 (10) 1790-1797
    CrossrefPubMedGoogle Scholar
  • 58 Vysokovsky A, Rosenberg N, Dardik R, Seligsohn U, Inbal A. Effect of four missense mutations in the factor XIII A-subunit gene on protein stability: studies with recombinant proteins. Blood Coagul Fibrinolysis 2006; 17 (2) 125-130
    CrossrefPubMedGoogle Scholar
  • 59 Birben E, Oner C, Oner R, Altay C, Gürgey A. Identification of an inframe deletion and a missense mutation in the factor XIIIA gene in two Turkish patients. Eur J Haematol 2003; 71 (1) 39-43
    CrossrefPubMedGoogle Scholar
  • 60 Mikkola H, Syrjälä M, Rasi V , et al. Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels. Blood 1994; 84 (2) 517-525
    PubMedGoogle Scholar
  • 61 Mikkola H, Yee VC, Syrjälä M , et al. Four novel mutations in deficiency of coagulation factor XIII: consequences to expression and structure of the A-subunit. Blood 1996; 87 (1) 141-151
    PubMedGoogle Scholar
  • 62 Kangsadalampai S, Chelvanayagam G, Baker R, Tiedemann K, Kuperan P, Board PG. Identification and characterization of two missense mutations causing factor XIIIA deficiency. Br J Haematol 1999; 104 (1) 37-43
    CrossrefPubMedGoogle Scholar
  • 63 Ichinose A, Tsukamoto H, Izumi T , et al. Arg260-Cys mutation in severe factor XIII deficiency: conformational change of the A subunit is predicted by molecular modelling and mechanics. Br J Haematol 1998; 101 (2) 264-272
    CrossrefPubMedGoogle Scholar
  • 64 Onland W, Böing AN, Meijer AB , et al. Congenital deficiency of factor XIII caused by two missense mutations in a Dutch family. Haemophilia 2005; 11 (5) 539-547
    CrossrefPubMedGoogle Scholar
  • 65 Jayandharan GR, Viswabandya A, Baidya S , et al. Mutations in coagulation factor XIII A gene in eight unrelated Indians. Five novel mutations identified by a novel PCR-CSGE approach. Thromb Haemost 2006; 95 (3) 551-556
    PubMedGoogle Scholar
  • 66 Souri M, Ichinose A. Impaired protein folding, dimer formation, and heterotetramer assembly cause intra- and extracellular instability of a Y283C mutant of the A subunit for coagulation factor XIII. Biochemistry 2001; 40 (45) 13413-13420
    CrossrefPubMedGoogle Scholar
  • 67 Souri M, Yee VC, Kasai K , et al. Novel Y283C mutation of the A subunit for coagulation factor XIII: molecular modelling predicts its impaired protein folding and dimer formation. Br J Haematol 2001; 113 (3) 652-654
    CrossrefPubMedGoogle Scholar
  • 68 Anwar R, Gallivan L, Miloszewski KJ, Markham AF. Factor XIII deficiency causing mutation, Ser295Arg, in exon 7 of the factor XIIIA gene. Thromb Haemost 2000; 84 (4) 591-594
    PubMedGoogle Scholar
  • 69 Gómez García EB, Poort SR, Stibbe J , et al. Two novel and one recurrent missense mutation in the factor XIII A gene in two Dutch patients with factor XIII deficiency. Br J Haematol 2001; 112 (2) 513-518
    CrossrefPubMedGoogle Scholar
  • 70 Mikkola H, Muszbek L, Haramura G, Hämäläinen E, Jalanko A, Palotie A. Molecular mechanisms of mutations in factor XIII A-subunit deficiency: in vitro expression in COS-cells demonstrates intracellular degradation of the mutant proteins. Thromb Haemost 1997; 77 (6) 1068-1072
    PubMedGoogle Scholar
  • 71 Anwar R, Gallivan L, Trinh C, Hill F, Markham A. Identification of a new Leu354Pro mutation responsible for factor XIII deficiency. Eur J Haematol 2001; 66 (2) 133-136
    CrossrefPubMedGoogle Scholar
  • 72 Ivaskevicius V, Windyga J, Baran B , et al. Phenotype-genotype correlation in eight Polish patients with inherited Factor XIII deficiency: identification of three novel mutations. Haemophilia 2007; 13 (5) 649-657
    CrossrefPubMedGoogle Scholar
  • 73 Izumi T, Nagaoka U, Saito T, Takamatsu J, Saito H, Ichinose A. Novel deletion and insertion mutations cause splicing defects, leading to severe reduction in mRNA levels of the A subunit in severe factor XIII deficiency. Thromb Haemost 1998; 79 (3) 479-485
    PubMedGoogle Scholar
  • 74 Anwar R, Miloszewski KJ, Markham AF. Identification of a large deletion, spanning exons 4 to 11 of the human factor XIIIA gene, in a factor XIII-deficient family. Blood 1998; 91 (1) 149-153
    PubMedGoogle Scholar
  • 75 Niiya T, Osawa H, Bando S , et al. A complete deficiency of coagulation factor XIII A-subunit due to a novel compound heterozygote of Ser 413 Leu missense and an nt 389 (ins G) frameshift mutation. Br J Haematol 1999; 107 (4) 772-775
    CrossrefPubMedGoogle Scholar
  • 76 Duan B, Wang X, Chu H , et al. Deficiency of factor XIII gene in Chinese: 3 novel mutations. Int J Hematol 2003; 78 (3) 251-255
    CrossrefPubMedGoogle Scholar
  • 77 Aslam S, Yee VC, Narayanan S, Duraisamy G, Standen GR. Structural analysis of a missense mutation (Val414Phe) in the catalytic core domain of the factor XIII(A) subunit. Br J Haematol 1997; 98 (2) 346-352
    CrossrefPubMedGoogle Scholar
  • 78 Kangsadalampai S, Yenchitsomanus P, Chelvanayagam G, Sawasdee N, Laosombat V, Board P. Identification of a new mutation (Gly420Ser), distal to the active site, that leads to factor XIII deficiency. Eur J Haematol 2000; 65 (4) 279-284
    CrossrefPubMedGoogle Scholar
  • 79 Anwar R, Gallivan L, Miloszewski KJ, Markham AF. Splicing and missense mutations in the human FXIIIA gene causing FXIII deficiency: effects of these mutations on FXIIIA RNA processing and protein structure. Br J Haematol 1998; 103 (2) 425-428
    CrossrefPubMedGoogle Scholar
  • 80 Takahashi N, Tsukamoto H, Umeyama H, Castaman G, Rodeghiero F, Ichinose A. Molecular mechanisms of type II factor XIII deficiency: novel Gly562-Arg mutation and C-terminal truncation of the A subunit cause factor XIII deficiency as characterized in a mammalian expression system. Blood 1998; 91 (8) 2830-2838
    PubMedGoogle Scholar
  • 81 Inbal A, Yee VC, Kornbrot N, Zivelin A, Brenner B, Seligsohn U. Factor XIII deficiency due to a Leu660Pro mutation in the factor XIII subunit-a gene in three unrelated Palestinian Arab families. Thromb Haemost 1997; 77 (6) 1062-1067
    PubMedGoogle Scholar
  • 82 Aslam S, Poon MC, Yee VC, Bowen DJ, Standen GR. Factor XIIIA Calgary: a candidate missense mutation (Leu667Pro) in the beta barrel 2 domain of the factor XIIIA subunit. Br J Haematol 1995; 91 (2) 452-457
    CrossrefPubMedGoogle Scholar
  • 83 Wu SY, Wang ZY, Dong NZ, Zhang W, Bai X, Ruan CG. [A novel genetic defect in a Chinese family with inherited coagulation factor XIII deficiency]. Zhonghua Xue Ye Xue Za Zhi 2006; 27 (3) 145-149
    PubMedGoogle Scholar
  • 84 Anwar R, Langlois S. The Arg703Trp missense mutation in F13A1 is a de novo event. Br J Haematol 2009; 146 (1) 118-120
    CrossrefPubMedGoogle Scholar
  • 85 Standen GR, Bowen DJ. Factor XIII ABristol 1: detection of a nonsense mutation (Arg171—>stop codon) in factor XIII A subunit deficiency. Br J Haematol 1993; 85 (4) 769-772
    CrossrefPubMedGoogle Scholar
  • 86 Zheng WD, Liu YH, He QY, Chen ZH, Fan XB, Liu HF. [Identification of Arg77Cys and Arg174stop double heterozygous mutation in a Chinese family with inherited FXIII deficiency]. Zhonghua Xue Ye Xue Za Zhi 2009; 30 (3) 158-161
    PubMedGoogle Scholar
  • 87 Anwar R, Gallivan L, Richards M, Khair K, Wright M, Minford A. Factor XIII deficiency: new nonsense and deletion mutations in the human factor XIIIA gene. Haematologica 2005; 90 (12) 1718-1720
    PubMedGoogle Scholar
  • 88 Kangsadalampai S, Farges-Berth A, Caglayan SH, Board PG. New mutations causing the premature termination of translation in the A subunit gene of coagulation factor XIII. Thromb Haemost 1996; 76 (2) 139-142
    PubMedGoogle Scholar
  • 89 Anwar R, Stewart AD, Miloszewski KJ, Losowsky MS, Markham AF. Molecular basis of inherited factor XIII deficiency: identification of multiple mutations provides insights into protein function. Br J Haematol 1995; 91 (3) 728-735
    CrossrefPubMedGoogle Scholar
  • 90 Kamura T, Okamura T, Murakawa M , et al. Deficiency of coagulation factor XIII A subunit caused by the dinucleotide deletion at the 5′ end of exon III. J Clin Invest 1992; 90 (2) 315-319
    CrossrefPubMedGoogle Scholar
  • 91 Aslam S, Bowen DJ, Mandalaki T, Gialeraki R, Standen GR. Factor XIII(A) subunit deficiency due to a homozygous 13-base pair deletion in exon 3 of the A subunit gene. Am J Hematol 1996; 53 (2) 77-80
    CrossrefPubMedGoogle Scholar
  • 92 Otaki M, Inaba H, Shinozawa K, Fujita S, Amano K, Fukutake K. [Characterization of a large deletion that leads to congenital factor XIII deficiency]. Rinsho Byori 2008; 56 (3) 187-194
    PubMedGoogle Scholar
  • 93 Trigui N, Frère C, D'Ercole C , et al. Molecular characterization of a novel mutation in the factor XIII A subunit gene associated with a severe defect and an adulthood diagnosis. Haemophilia 2007; 13 (2) 221-222
    CrossrefPubMedGoogle Scholar
  • 94 Kangsadalampai S, Chelvanayagam G, Baker RT , et al. A novel Asn344 deletion in the core domain of coagulation factor XIII A subunit: its effects on protein structure and function. Blood 1998; 92 (2) 481-487
    PubMedGoogle Scholar
  • 95 Aslam S, Standen GR, Bruce LJ, Gialeraki R, Mandalaki T. A novel insertion mutation (1286insC) in exon 9 of the factor XIII-A subunit gene. Blood Coagul Fibrinolysis 1998; 9 (5) 441-443
    CrossrefPubMedGoogle Scholar
  • 96 Jiao WY, Wu JS, Ding QL , et al. [Identification of a novel mutation of F (13) A gene in a pedigree with factor XIII deficiency]. Zhonghua Xue Ye Xue Za Zhi 2007; 28 (9) 598-601
    PubMedGoogle Scholar
  • 97 Birben E, Oner R, Oner C, Gümrük F, Altay C, Gürgey A. Mutations in coagulation factor XIII A gene in three Turkish patients: two novel mutations and a known insertion. Br J Haematol 2002; 118 (1) 278-281
    CrossrefPubMedGoogle Scholar
  • 98 Mikkola H, Muszbek L, Laiho E , et al. Molecular mechanism of a mild phenotype in coagulation factor XIII (FXIII) deficiency: a splicing mutation permitting partial correct splicing of FXIII A-subunit mRNA. Blood 1997; 89 (4) 1279-1287
    PubMedGoogle Scholar
  • 99 Vreken P, Niessen RW, Peters M, Schaap MC, Zuithoff-Rijntjes JG, Sturk A. A point mutation in an invariant splice acceptor site results in a decreased mRNA level in a patient with severe coagulation factor XIII subunit A deficiency. Thromb Haemost 1995; 74 (2) 584-589
    PubMedGoogle Scholar
  • 100 Maak B, Kochhan L, Heuchel P, Jenderny J. FXIII deficiency due to base exchange Thr 449 (ACT) —> Ile (ATT) in exon 11 of the factor 13A gene. A cause of bleeding?. Hamostaseologie 2010; 30 (3) 162-164
    PubMedGoogle Scholar
  • 101 Khalife H, Muwakkit S, Al-Moussawi H , et al. Spontaneous splenic rupture in a patient with factor XIII deficiency and a novel mutation. Pediatr Blood Cancer 2008; 50 (1) 113-114
    CrossrefPubMedGoogle Scholar
  • 102 Morange P, Trigui N, Frère C , et al. Molecular characterization of a novel mutation in the factor XIII a subunit gene associated with a severe defect: importance of prophylactic substitution. Blood Coagul Fibrinolysis 2009; 20 (7) 605-606
    CrossrefPubMedGoogle Scholar
  • 103 Souri M, Yee VC, Fujii N, Ichinose A. Molecular modeling predicts structural changes in the A subunit of factor XIII caused by two novel mutations identified in a neonate with severe congenital factor XIII deficiency. Thromb Res 2012; 130 (3) 506-510
    CrossrefPubMedGoogle Scholar
  • 104 Castaman G, Giacomelli SH, Schroeder V , et al. Further evidence of heterogeneity of gene defects in Italian families with factor XIII deficiency. Haemophilia 2012; 18 (1) e6-e8
    CrossrefPubMedGoogle Scholar
  • 105 Shanbhag S, Shetty S, Ghosh K. Mutations in coagulation factor XIII subunit A in severe factor XIII deficiency patients: five novel mutations detected. Haemophilia 2011; 17 (5) e843-e845
    PubMedGoogle Scholar
  • 106 Ichinose A, Davie EW. Characterization of the gene for the a subunit of human factor XIII (plasma transglutaminase), a blood coagulation factor. Proc Natl Acad Sci U S A 1988; 85 (16) 5829-5833
    CrossrefPubMedGoogle Scholar