Identification of four novel mutations in F5 associated with congenital factor V deficiency

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• 作者：Sachiko Kanaji (1)
  Taisuke Kanaji (1) (2)
  Miho Honda (3)
  Sachie Nakazato (3)
  Kazuo Wakayama (3)
  Yoshitomi Tabata (3)
  Shoichiro Shibata (4)
  Hisashi Gondo (4)
  Ikuko Nakamura (5)
  Koichi Node (5)
  Masanori Miura (6)
  Masaharu Miyahara (6)
  Takashi Okamura (2)
  Fumio Nagumo (3)
  Shoichiro Ohta (7)
  Kenji Izuhara (1) (7)
  
• 关键词：Coagulation factors ; Congenital coagulation disorders ; Gene mutations
• 刊名：International Journal of Hematology
• 出版年：2009
• 出版时间：January 2009
• 年：2009
• 卷：89
• 期：1
• 页码：71-75
• 全文大小：300KB
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  3. Kane WH, Davie EW. Blood coagulation factors V and VIII: structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders. Blood. 1988;71:539-5.
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  10. Montefusco MC, Duga S, Asselta R, Malcovati M, Peyvandi F, Santagostino E, et al. Clinical and molecular characterization of 6 patients affected by severe deficiency of coagulation factor V: Broadening of the mutational spectrum of factor V gene and in vitro analysis of the newly identified missense mutations. Blood. 2003;102:3210-. doi:10.1182/blood-2003-03-0922 . CrossRef
  11. Schrijver I, Hong DW, Mandle L, Jones CD, DiMichele D, Monahan PE, et al. High frequency of premature termination mutations in the factor V gene: three factor V deficiency case reports and a mutation review. Thromb Haemost. 2005;93:610-.
  12. Ajzner EE, Balogh I, Szabo T, Marosi A, Haramura G, Muszbek L. Severe coagulation factor V deficiency caused by 2 novel frameshift mutations: 2952delT in exon 13 and 5493insG in exon 16 of factor 5 gene. Blood. 2002;99:702-. doi:10.1182/blood.V99.2.702 . CrossRef
  13. Hentze MW, Kulozik AE. A perfect message: RNA surveillance and nonsense-mediated decay. Cell. 1999;96:307-0. doi:10.1016/S0092-8674(00)80542-5 . CrossRef
  14. Adams TE, Hockin MF, Mann KG, Everse SJ. The crystal structure of activated protein C-inactivated bovine factor Va: implications for cofactor function. Proc Natl Acad Sci USA. 2004;101:8918-3. doi:10.1073/pnas.0403072101 . CrossRef
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• 作者单位：Sachiko Kanaji (1)
  Taisuke Kanaji (1) (2)
  Miho Honda (3)
  Sachie Nakazato (3)
  Kazuo Wakayama (3)
  Yoshitomi Tabata (3)
  Shoichiro Shibata (4)
  Hisashi Gondo (4)
  Ikuko Nakamura (5)
  Koichi Node (5)
  Masanori Miura (6)
  Masaharu Miyahara (6)
  Takashi Okamura (2)
  Fumio Nagumo (3)
  Shoichiro Ohta (7)
  Kenji Izuhara (1) (7)
  
  1. Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, 849-8501, Japan
  2. Division of Hematology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, 830-0011, Japan
  3. Clinical Laboratory, The Medical School Hospital, Saga Medical School, Saga, 849-8501, Japan
  4. Department of Internal Medicine, Saga Prefectural Hospital Koseikan, 1-12-9 Mizugae, Saga, 840-8571, Japan
  5. Department of Cardiovascular and Renal Medicine, Saga Medical School, Saga, 849-8501, Japan
  6. Department of Internal Medicine, Karatsu Red Cross Hospital, 1-5-1 Futago, Karatsu, Saga, 847-8588, Japan
  7. Department of Laboratory Medicine, Saga Medical School, Saga, 849-8501, Japan
  

文摘

Coagulation factor V (FV) deficiency is a rare bleeding disorder characterized by low coagulant and antigen levels of FV with bleeding symptoms ranging from mild to severe. Only a limited number of mutations have been reported because of the large size of the factor V gene (F5) as well as the low prevalence. In this study, we have identified four novel mutations in F5 in five unrelated patients with congenital FV deficiency. All the patients, including two with undetectable FV activity, were asymptomatic and were found to have prolonged prothrombin time and activated partial thromboplastin time during preoperative screening or routine examinations. All four mutations found in this study are either missense or in-frame deletion. This is in contrast with previous reports of a high frequency of mutations introducing premature termination codons in inherited FV deficiency. Missense mutations of F5 might produce a mild phenotype and are not frequently diagnosed. Although FV deficiency is a very rare disorder with a predicted incidence of one in 1?million, this study suggests that the numbers of F5 mutations, especially missense mutations, are higher than estimated.