Molecular defects in hemophilia A: identification and characterization of
mutations in the factor VIII gene and family analysis
M Higuchi, L Kochhan, R Schwaab, H Egli, HH Brackmann, J Horst and K Olek
Institut fur Klinische Biochemie, Universitat Bonn, FRG.
Hemophilia A is an X-linked bleeding disorder caused by a deficiency or
abnormality of factor VIII, affecting approximately 1 male in 10,000. A
subgroup of the patients develops inhibitors against factor VIII during
substitution therapy. Because a considerable percentage of all cases is
thought to result from de novo mutations, it is likely that many different
molecular lesions lead to hemophilia A. In order to understand the
molecular basis of this disorder, we examined 160 patients with different
clinical features using factor VIII gene probes. We could identify six
different deletions and seven nonsense mutations within the factor VIII
gene. Family analysis revealed that five of these mutations occurred de
novo within two generations; two of them arose in the maternal grandfather
and three in the mother. In one of these mothers we could identify a
mitotic origin. Mapping of the deletions showed no deletion-prone region
within the gene. Furthermore, we could not find any correlation between the
particular gene defects and "inhibitor" phenotypes.
Volume 74,
Issue 3,
pp. 1045-1051,
08/15/1989
Copyright © 1989 by The American Society of Hematology
