International Journal of Hematology

, Volume 79, Issue 3, pp 303–306 | Cite as

Inversions of the Factor VIII Gene in Japanese Patients with Severe Hemophilia A

  • Kazuyoshi Fukuda
  • Hiroyuki Naka
  • Shogo Morichika
  • Masaru Shibata
  • Ichiro Tanaka
  • Midori Shima
  • Akira Yoshioka
Case Report


Hemophilia A is genetically very heterogeneous because disease-causing mutations involving deletions, point mutations, insertions, and inversions are scattered throughout the factor VIII gene. Of these mutations, inversions, which are intrachromosomal recombinations between int22h- 1 (intron 22 homologous region 1) and 1 of 2 other extragenic copies located 500 kilobases upstream, are the more frequently found defects, especially in patients with severe hemophilia A. Reportedly, approximately half of all severe hemophilia A patients have inversions in intron 22. A group of unrelated patients from the middle of Japan with severe hemophilia A were screened by Southern blot analysis for gene inversions. Forty-two of 100 severely affected patients presented factor VIII gene rearrangements. Of these patients, 36 exhibited the distal type of inversion, and 6 exhibited the proximal type. No other variant type of recombination was observed. In this study, neither the prevalence of inhibitor development against factor VIII nor the frequency of sporadic cases in the group presenting gene inversions was significantly different from that in the group without chromosomal inversions. Southern blot analysis successfully detected a carrier in a hemophilia family for which no patient was available. Genetic counseling of patients with severe hemophilia A and their families will be considerably improved, because the inversions occur in 42% of the Japanese patients with severe hemophilia.

Key words

Hemophilia A nhibitor Inversion Carrier detection 


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Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Kazuyoshi Fukuda
    • 1
  • Hiroyuki Naka
    • 1
  • Shogo Morichika
    • 1
  • Masaru Shibata
    • 1
  • Ichiro Tanaka
    • 1
  • Midori Shima
    • 1
  • Akira Yoshioka
    • 1
  1. 1.Department of PediatricsNara Medical UniversityNaraJapan

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