title: Inversions of the factor VIII gene in Swedish patients with severe haemophilia A.
abstract: The series comprised 49 Swedish patients with severe haemophilia A [belonging to 49 families (21 with known and 28 with sporadic haemophilia)], of whom 12 had developed F. VIII inhibitors. Using Southern blotting, 45% (22/49) were found to have inversions, i.e., intrachromosomal rearrangements of the tip of the X-chromosome. Twenty patients had one or the other of the two variants of inversions recently published, whereas 2 patients manifested novel band patterns. Inversions were found in 50% of the families with sporadic haemophilia, and in 38% of those with known haemophilia. Fourteen families with sporadic haemophilia A had inversions, the proband carrying the de novo mutation in 4 cases and the proband's mother in 10 cases. Six inversions derived from a male and five from a female X-chromosome meiosis, the origin of the remaining three was not established. Genetic counselling of patients with severe haemophilia A and their families will be considerably improved, as inversions occur in half the severe cases and can be detected by a simple Southern blotting procedure.
authors.affiliation: Department of Paediatrics, University of Lund, Malmö General Hospital, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Ljung
authors.forename: E
authors.initials: E
authors.lastname: Sjörin
mesh_terms: D007446:Chromosome Inversion; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D013548:Sweden; D014960:X Chromosome
chemical_list: D005169:Factor VIII