MILD HEMOPHILIA-A IN ICELAND - CLINICAL GENETIC-STUDIES OF 3 FAMILIESWITH THE SAME MUTATION

Objectives. The aim of the study was to define the phenotype in three families with mild haemophilia A and to determine restriction fragment length polymorphisms (RFLP), which could support a hypothesis of a co mmon progenitor of the families. Design. Family survey. Setting. Index cases were identified in and outside hospital and a family survey for symptoms and signs of bleeding in family members and sampling for coa gulation and RFLP studies were mostly carried out in the field. Subjec t. Family members with and without symptoms of bleeding were selected for investigation and normal spouses and unrelated individuals were in vestigated for control. Interventions. Medical advice regarding affect ed family members were given to the families and their physicians. Mai n outcome measures. Bleeding time, factor VIII activity, quantificatio n of factor VIII:Ag, von Willebrand factor (vWF) Ag and vWF ristocetin assay. Typing of RFLP polymorphisms for genetic homogeneity. Results. Bleeding manifestations are present in both sexes in the three famili es although more frequent and more severe in the males. The level of f actor VIII activity is between 10 and 20% in most affected males where as 35-60% is found approximately in 2/3 of female carriers and in 1/3 of them factor VIII activity is within the normal range. It is suggest ed that screening for this mild haemophilia A gene by a molecular gene tic method would be of clinical value now, its mutation having been de tected. Conclusions. Transmission of mild haemophilia A through six to seven generations is demonstrated by the study. The mild haemophilia A type described is the most prevalent of haemophilia A types in Icela nd (population 260 000, 1992). The founder effect was confirmed by stu dies of RFLP polymorphisms.