Spectrum of molecular defects and mutation detection rate in patients with mild and moderate hemophilia A

Abstract

The amount of residual factor VIII (FVIII:C) determines the clinical variability of hemophilia A. About 50% of the patients have severe hemophilia A with a FVIII:C activity less than 1% of normal. Moderate (FVIII:C 2-5% of normal) and mild (FVIII:C > 5% of normal) hemophilia A occur in about 10% and 30-40% of patients, respectively. Recently we showed that the mutation detection rate in severely affected male patients is virtually 100% when testing for the common intron 22-/intron 1-inversions and big deletions, followed by genomic sequencing of the F8 gene. We also showed that protein truncating molecular defects are prevalent in those patients [1].Here we report on the mutation detection rate and the spectrum of mutations in 136 patients with mild/moderate hemophilia A, as well as their distribution throughout the F8 protein. © 2007 Springer Verlag Berlin Heidelberg.