Carrier detection in the haemophilias

• Main Author: Perry, David James
• Published: University of Edinburgh 1992
• Subjects: 616.042
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.660543

<i>Haemophilia A</i>: 44 families with haemophilia A have been studied comprising 107 males and 125 females. Of the males 53 were haemophiliacs and of these 37 had severe (VIII:C < 0.01iu/dl), 7 had moderate disease (VIII:C > 0.01 but < 0.05iu/dl) and 9 had mild disease (VII:C > 0.05iu/dl). From pedigree analysis 40 women could be established as obligatory carriers, 5 women were considered to be normal and the remaining 80 women were potential carriers. In 22 families the disease appeared to have arisen spontaneously whilst in the remaining 22 there was a family history of haemophilia. Phenotypic analysis using VIII:C vWF:Ag vWF:RCo assays and the ratios VIII:C/vWF:Ag, VIII:C/vWF:RCo were used to identify carriers and the results compared to those obtained using genotypic analysis with 3 intragenic (Bcl I, Bgl I, Xba I) and 2 extragenic (Taq I, Bgl II) restriction fragment length polymorphisms. A control group of 31 age-matched normal females and obligatory carriers were used as controls to establish values for the measurements of VIII:C/vWF:Ag and VIII:C/vWF:RCO ratios which correctly classified all the normal women. Evaluation of the VIII:C/vWF:Ag and VIII:C/vWF:RCo ratios in the control group demonstrated the VIII:C/vWF:Ag ratio to be superior, correctly classifying 77% of the obligate carrier compared to only 42% using the VIII:C/vWF:RCo ratio. Of the 40 obligate carriers 26/37 were shown to have an abnormal coagulation phenotype, 11 to have a normal phenotype and in 3 no coagulation data was available. 27 of the potential carriers had an abnormal coagulation phenotype, 47 were normal and in 6 no data was available. <i>Haemophilia B</i>: 5 families with haemophilia have been studied comprising 11 males and 12 females. Of the males 4 were haemophiliacs (IX:C > 0.01iu/dl). Of the 12 females, 3 could be classified as obligate carriers, 8 as potential carriers and 1 as a probable haemophilac female from pedigree data. Although the mean IX:C for the obligatory carriers was lower than that of the control group, there was a considerable overlap of values. Only limited phenotypic data was available but 2 of 3 obligate carriers and 3 of 4 potential carriers had IX:C assays below the lowest value obtained in a control group of 15 normal women suggesting carriership. No CRM* families were identified.