S. Windsor et al., SEVERE HEMOPHILIA-A IN A FEMALE RESULTING FROM 2 DE-NOVO FACTOR-VIII MUTATIONS, British Journal of Haematology, 90(4), 1995, pp. 906-909
A 2-year-old girl is described with severe haemophilia A (factor VIII:
C <0.01 units/ml). Both of her parents were phenotypically normal. Cyt
ogenetic analysis on the proband demonstrated an interstitial X chromo
some deletion encompassing Xq26-q28. Molecular studies with several po
lymorphic markers close to and within the factor Vm gene showed that t
he proband had inherited only the paternal factor Vm gene, indicating
that the X chromosome deletion had occurred de novo in the maternal ge
rm line. Further study of the factor VIII gene inherited by the proban
d from her father showed the presence of a de novo gene inversion muta
tion (a type 1, distal pattern inversion). Neither parent showed any e
vidence of the factor VIII inversion in their somatic DNA. The severe
haemophilia A documented in this girl is therefore the result of two d
e novo mutations affecting the factor Vm gene, a maternally derived X
chromosome deletion and a paternal factor VIII inversion mutation.