W. Schroder et al., HEMOPHILIA-B IN FEMALE TWINS CAUSED BY A POINT MUTATION IN ONE FACTOR-IX GENE AND NONRANDOM INACTIVATION PATTERNS OF THE X-CHROMOSOMES, Thrombosis and haemostasis, 78(5), 1997, pp. 1347-1351
Haemophilia B is a X-linked recessive bleeding disorder with an incide
nce of 1:25,000-30,000 male birth. Usually female carriers are clinica
lly normal. Phenotypic expression of the disease in female carriers is
extremely rare. We describe cytogenetically inconspicuous female iden
tical twins both with factor IX levels below 2%, prolonged bleeding af
ter veni-puncture as well as haematomas after intramuscular injections
. The father, suffering from a severe haemophilia B, is deceased. By s
equencing one point mutation was characterized in heterozygote conditi
on in the factor IX gene of the probands at nt 17678. This mutation le
ads to the substitution cystein 88 to tyrosine in the growth factor do
main 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 M27 beta indicated a nonrandom pattern of X-chromosomal inactiv
ation 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.