Prenatal diagnosis of haemophilia: A preliminary report

Background. Haemophilia A is the most common congenital bleeding disorder s een in man, affecting one in 5000 to 10 000 males. Because of the large siz e and heterogeneity of mutations in the factor VIII gene, direct detection of mutations is not practically feasible, except the recently detected intr on 22 inversions. Hence, the indirect method of gene tracking using various polymorphic markers is the method of choice. Using this approach, we have performed antenatal diagnosis in four haemophilia A families. Methods. The four families included 21 subjects who were used for gene-trac king analysis. Two families had a positive history with more than one membe r affected, while the remaining two families had a negative history with on ly one affected son. In all four families, the propositi and their affected relatives had severe haemophilia A with factor VIII:C less than 1%. All we re negative for inhibitors. The polymorphic markers used were IVS 18 Bcl I, IVS 19 Hind III and the extragenic DXS 52 St 14 of the factor VIII gene. P rior to polymorphism analysis, the sex of the foetus was determined using Y chromosome-specific primers, Ail the analyses were carried out by polymera se chain reaction, Results. Antenatal diagnosis in the four families showed three normal male foetuses and one normal female foetus, Two families provided evidence with only IVS 18 Bcl I and St 14 markers. One family provided information with o nly intron 19 Hind III marker. The fourth family provided information with all three markers, The coagulation parameters were almost in agreement with the results of DNA analysis, Conclusion. All three polymorphic markers yielded information. This suggest s that these three markers can be effectively used in the antenatal diagnos is of haemophilia A in Indian families.