More Than Half the Sporadic Cases of Hemophilia A in Sweden Are Due to a Recent Mutation

ABSTRACT. The aim of this study was to ascertain how many of the sporadic cases of severe Haemophilia A in Sweden are due to recent mutation, and establish its origin. DNA analysis was performed in 18 randomly selected families with a sporadic case of severe haemophilia A. Restriction fragment length polymorphism (RFLP) patterns were investigated, two intragenic (Bcl I, Xba I/Kpn I) and two extragenic (DX 13, St 14) RFLP being used. In 10/18 families a haemophilia‐linked gene was found to have derived from the healthy maternal grandfather; on the basis of clotting and immunological assay results, the odds were high (> 104:1) for maternal carriership in four of these 10 cases, and for maternal non‐carriership in two, four being indeterminate. In 4/18 families a haemophilia‐linked gene derived from the healthy maternal grandmother; according to clotting and immunological assay results, in two cases the odds were high for maternal non‐carriership. In the remaining 4/18 families no conclusions could be drawn from the RFLP pattern as to the origin of mutation. We conclude that at least 55 % of the sporadic cases of severe hemophilia A in Sweden are due to a recent mutation within the last two genrations.

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