Severe haemophilia A in a female resulting from two de novo factor VIII mutations.
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. Cytogenetic analysis on the proband demonstrated an interstitial X chromosome deletion encompassing Xq26-q28. Molecular studies with several polymorphic markers close to and within the factor VIII gene showed that the proband had inherited only the paternal factor VIII gene, indicating that the X chromosome deletion had occurred de novo in the maternal germ line. Further study of the factor VIII gene inherited by the proband from her father showed the presence of a de novo gene inversion mutation (a type 1, distal pattern inversion). Neither parent showed any evidence of the factor VIII inversion in their somatic DNA. The severe haemophilia A documented in this girl is therefore the result of two de novo mutations affecting the factor VIII gene, a maternally derived X chromosome deletion and a paternal factor VIII inversion mutation.
Windsor
S
S
Department of Pathology, Queen's University, Kingston, Ontario, Canada.
Lyng
A
A
Taylor
S A
SA
Ewenstein
B M
BM
Neufeld
E J
EJ
Lillicrap
D
D
D015139:Blotting, Southern; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D007223:Infant; D009154:Mutation; D010375:Pedigree
D005169:Factor VIII