Value of DNA analysis with multiple DNA probes for the detection of hemophilia A carriers

Detection of hemophilia carriers is an important issue and should be addressed with great care. The allelic frequencies of three intragenic probes (Bcl I for probe p114.12, Xba I for probe p482.6, and Bgl I for probe C) and one linked probe (Bgl II for probe DX 13) are reported, together with their diagnostic yield singly and in combination. In this series, 725 individuals (405 females) in 156 families were analyzed for restriction fragment-length polymorphisms. A total of 255 females (63%) were found to be informative for their carrier state with one or more probes. The most informative intragenic probe was p482.6 (useful in 49% of informative females). The most informative probe was DX 13 (useful in 59% of informative females), but this is a linked probe that carries a 5% risk of cross-over. By the use of probes p114.12, p482.6, and DX 13, almost 98% of all the informative females could be detected. In about 71% of families with a family history and a known carrier, prenatal diagnosis was feasible.