Summary
We performed DNA analysis in 20 families with haemophilia A in order to evaluate its
usefulness for carrier detection and prenatal diagnosis.
The polymorphic Bell site within intron 18 of the factor VIII gene and the extragenic
TaqI and Bglll polymorphic sites which are detected by the random DNA probes designated
St 14 and DX13, respectively, were investigated for.
Two events of recombination were found between the St 14 and the haemophilia A locus
in 51 informative meioses. In one of these recombinant meioses crossing over had also
occurred between the DX13 and the haemophilia A locus. No further crossovers between
the DX13 and the haemophilia A locus were found in 20 informative meioses.
Segregation analysis of the polymorphic markers and the deleterious mutation within
the families allowed a diagnosis at the gene level for 52 out of 57 potential carriers.
The new method considerably decreased the uncertainty about carriership for seventeen
of the nineteen women with a probability of carriership between 5% and 95% based on
pedigree analysis and factor VIII assays.
In seven cases chromosome and DNA analysis of a chorionic villus biopsy was carried
out. Three of the fetuses were female, four were male. Three of the male fetuses had
inherited the normal maternal X-chromosome and were, therefore, not affected. For
another male fetus no diagnosis at the gene level was possible since the mother was
homozygous for all the known restriction fragment length polymorphisms within or closely
linked with the haemophilia A locus.
Keywords
Carrier detection - Haemophilia A - Prenatal diagnosis - Restriction fragment length
polymorphisms
