title: Screening for inversions in the factor VIII (F8) gene causing severe haemophilia A.
abstract: A total of 164 unrelated patients with severe haemophilia A were screened for partial inversions of the factor VIII (F8) gene resulting from recombination between the intronic F8A gene and one or other of two homologous upstream A gene sequences. Inversions were found in 69 (42%) patients. Most inversions (90%) involved the distal rather than the proximal A gene. This unique mutational mechanism is estimated to occur with a frequency of 7.2 x 10(-6) per gene per gamete per generation. Although two patients with an inversion possessed inhibitors (antibodies) against factor VIII, possession of inhibitors did not appear to be associated disproportionately with inversion-type mutations.
authors.affiliation: Charter Molecular Genetics Laboratory, Thrombosis Research Institute, London, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Millar
authors.forename: V V
authors.initials: VV
authors.lastname: Kakkar
authors.forename: D N
authors.initials: DN
authors.lastname: Cooper
mesh_terms: D015139:Blotting, Southern; D007446:Chromosome Inversion; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D008297:Male; D011995:Recombination, Genetic; D012016:Reference Values
chemical_list: D005169:Factor VIII