Screening for inversions in the factor VIII (F8) gene causing severe haemophilia A.
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.
Millar
D S
DS
Charter Molecular Genetics Laboratory, Thrombosis Research Institute, London, UK.
Kakkar
V V
VV
Cooper
D N
DN
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
D005169:Factor VIII