Summary
Haemophilia B is a X-linked recessive bleeding disorder with an incidence of 1:25,000-30,000
male birth. Usually female carriers are clinically normal. Phenotypic expression of
the disease in female carriers is extremely rare.
We describe cytogenetically inconspicuous female identical twins both with factor
IX levels below 2%, prolonged bleeding after venipuncture as well as haematomas after
intramuscular injections. The father, suffering from a severe haemophilia B, is deceased.
By sequencing one point mutation was characterized in heterozygote condition in the
factor EX gene of the probands at nt 17678. This mutation leads to the substitution
cystein 88 to tyrosine in the growth factor domain of the factor IX. Investigation
of the X-chromosomal inactivation by comparison of methylation patterns of genomic
DNA at locus DXS255 after digestion with Pst I and Pst I +Hha I and hybridisation
with the probe M27β indicated a nonrandom pattern of X-chromosomal inactivation in
the twins. In both girls, only the paternal X-chromosome was the active one leading
to the phenotypic expression of haemophilia in the female carriers.
