The molecular genetic analysis of haemophilia A; characterization of six partial deletions in the factor VIII gene

In a survey of 528 unrelated haemophilia A patients, six partial deletions of the factor VIII (FVIII) gene were detected by Southern blotting. These deletions were further mapped by a combination of Southern blotting and polymerase chain reaction amplification and found to vary in length between 4.7kb and 57kb. The frequency of detectable FVIII gene deletions (about 1%) is thus considerably lower than previously reported. Statistical analysis of currently available data did not provide any evidence for a deletion “hotspot”. Four of the six deletion patients reported here possessed inhibitors. Taken together with previous data, deletion of the FVIII gene was found to be associated with an approximately fivefold higher risk of developing inhibitors compared with other severe haemophiliacs without gene deletions