• Jyh-Pyng Gau, Hui-Chi Hsu, Chao-Hung Ho, Wing-Keung Chau, Chih-Cheng Chen, and Jie-Yu You.
• Division of Hematology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. jpgau@vghtpe.gov.tw
• J Chin Med Assoc. 2003 Sep 1; 66 (9): 518-22.

BackgroundHemophilia A is caused by mutations in the gene for coagulation factor VIII. Recently, it has been reported that about half of the patients with severe hemophilia A have a large genomic inversion of the factor VIII gene. We tried to use a rapid method to detect this important mutation in the Chinese hemophiliacs.MethodsBased on amplification of the leaky mRNA of factor VIII gene in peripheral blood lymphocytes, a reverse-transcription polymerase chain reaction (RT-PCR) method was applied to detect the inversion of intron 22 in the Chinese patients with severe hemophilia A.ResultsThis mutation was detected in 7 of 20 (35%) severe hemophilia A patients from unrelated families. The mutation was not found in 3 patients of non-severe hemophilia A and 4 normal controls. Family history of bleeding tendency could not be traced in 3 of the 7 patients with intron 22 inversion.ConclusionsIntron 22 inversion of the factor VIII gene is the major genetic mutation for severe hemophilia A in Taiwan. There is a high probability of de novo mutation for this genetic change. The results were consistent with the concept that intron 22 inversion will always result in severe deficiency of factor VIII. Rapid detection of this common mutation can helpfully guide the direction of molecular study in genetic counselling.

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