HEMOPHILIA A: EXPERIENCE WITH PRENATAL DIAGNOSIS AND CARRIER DETECTION USING DNA ANALYSIS

Abstract

Prenatal diagnosis and carrier detection of hemophilia A using DNA analysis has been attempted in 113 families since February 1985. DNA polymorphisms within and linked to the factor VIII (F8) gene were used as markers for the defective FB gene in these families. When possible, diagnosis was preferentially based on DNA markers within the F8 gene, while in about 25% of families, diagnosis was based on DNA markers linked to the F8 (theoretical error rate in these latter cases is 1-5%). The results of these studies are as follows: Prenatal Diagnosis: 64 families. Diagnoses made: 45 (normal males: 20, affected males: 14, carrier females: 5, noncarrier females: 6). Diagnoses not made: 26 [Because a) the carrier status of a female fetus was not requested, b) pregnancy was terminated prior to testing, or c) family was noninformative in the initial phase of the study because of lack of DNA polymorphism markers].Carrier testing: 72 families (carriers: 33, noncsrriers: 28, noninformative families: 4, new mutations to hemophilia: 5, incomplete linkage analyses: 2).These data suggest that carrier detection and prenatal diagnosis of hemophilia A using the present DNA polymorphisms is possible in most but not all families at risk. Additional DNA polymorphisms within the F8 gene are needed to further improve the efficacy and eliminate the possibility of error in diagnosis due to the recombination distance of some DNA markers from the F8 gene.