Summary
Hemophilia B is an X-linked bleeding disorder. We report on female twins, who were
conspicious in prolonged bleeding after venipuncture as well as hematomas after intramuscular
injections even in the first months of their life. Their father suffering from a severe
hemophilia B deceased in 1992. Their mother, half-brother and grandmother from their
father’s side had no signs of bleeding disorders. Clotting analysis performed in both
twins revealed a markedly prolonged partial thromboplastin time (>100 s). The factor
IX levels were below 2%. In order to detect mutations, a general screen using the
polymerase chain reaction (PCR) followed by single strand conformation polymorphism
(SSCP) analysis of the PCR products have been performed. PCR products have been cut
into smaller fragments using restriction endonucleases (RE) for an in-depth SSCP screen.
A general screen for gross abnormalities in the factor IX gene including deletions,
insertions and rearrangements was performed by Southern blot analysis of RE-digests
of genomic DNA using the factor IX cDNA as a hybridization probe. Furthermore, we
screened for mutations in the CG dinucleotides comprising part of RE-recognition sequences
(exon 1, 2, 3, 4, 5, and 8). By all methods applied herein, no mutations have been
detected in these twins. On the basis of our results the hemophilia B of these twins
might be explained by extreme non-random lyonization.
