INVERSIONS OF THE FACTOR-VIII GENE IN SWEDISH PATIENTS WITH SEVERE HEMOPHILIA-A

The series comprised 49 Swedish patients with severe haemophilia A [be longing to 49 families (21 with known and 28 with sporadic haemophilia )], of whom 12 had developed F.VIII inhibitors. Using Southern blottin g, 45% (22/49) were found to have inversions, i.e., intrachromosomal r earrangements of the tip of the X-chromosome. Twenty patients had one or the other of the two variants of inversions recently published, whe reas 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 a nd the proband's mother in 10 cases. Six inversions derived from a mal e and five from a female X-chromosome meiosis, the origin of the remai ning three was not established. Genetic counselling of patients with s evere 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.