Factor VIII gene deletion in a Thai hemophilia A patient
P. Pung amritt', A. Treesucon', S. Petrarat', G. Veerakul, C. Mahasandana' and P.T. Yenchitsornanus'*
Hematology Unit, Department of Pediatrics, 'Division of Medical Genetics, Department of Medicine, 'Molecular Genetic and Medical Molecular Biology Units, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
(Received 20 January 1998 / Accepted 3] July 1998)
Abstract.
Hemophilia A is a common X linked recessive bleeding disorder caused by abnormal factor VIII gene, resulting in deficiency of clotting factor VIII protein. The factor VIII gene consists of 26 exons and spans about 186 kilobase DNA. Different types of mutations in the factor VIII gene including inversions, point mutations, deletions, and insertions have been described. The most common mutation in severe hemophilia A patients is the inversion involving exons 1-22 of the factor VIII gene. Mutations causing hemophilia A in Thai patients are being characterized with the aim to understand molecular defects of the disease and to develop direct methods for carrier detection and prenatal diagnosis by DNA technique. Here, we report the first example of the factor VIII gene deletion found in a severe Thai hemophilia A patient. The gene deletion in this patient was observed from screening DNA samples of Thai hemophilia A patients with multiplex PCR developed to simultaneously amplify DNA sequences in 7 exons of the gene. The extent of factor VIII gene deletion in this patient was found to involve DNA region of about 2.2 kb covering exon 26 and the 3' non coding sequence of the factor VIII gene.
Keywords: factor VIII, gene deletion, hemophilia, multiplex PCR, mutation, Thai
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