title: Severe haemophilia A in a female resulting from two de novo factor VIII mutations.
abstract: 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.
authors.affiliation: Department of Pathology, Queen's University, Kingston, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Windsor
authors.forename: A
authors.initials: A
authors.lastname: Lyng
authors.forename: S A
authors.initials: SA
authors.lastname: Taylor
authors.forename: B M
authors.initials: BM
authors.lastname: Ewenstein
authors.forename: E J
authors.initials: EJ
authors.lastname: Neufeld
authors.forename: D
authors.initials: D
authors.lastname: Lillicrap
mesh_terms: D015139:Blotting, Southern; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D007223:Infant; D009154:Mutation; D010375:Pedigree
chemical_list: D005169:Factor VIII