A reliable method for determination of carrier status and genetic counselli
ng is required for effective control of haemophilia. Linkage analysis is cu
rrently the most widely used method for this purpose; however, in cases whe
re there is no prior family history and/or unavailability of informative po
lymorphic markers it is less applicable. Detection of a mutation characteri
zed in each family may be an alternative method for determination of the ca
rrier status. In this study, linkage analysis using four polymorphic DNA ma
rkers, and direct mutation analysis were compared to determine the carrier
status in six unrelated Thai haemophilia A families, two with a family hist
ory and four without. In the two families with a family history of haemophi
lia A, the carrier and noncarrier statuses could readily be determined in e
ight females by either linkage or direct mutation analysis. In the four fam
ilies without a family history, the polymorphic DNA markers for linkage ana
lysis were informative in two families and uninformative in the other two.
The carrier status could be excluded in all four female siblings of the pat
ients in the former. However, the specific FVIII gene mutation was not obse
rved in the mother of one patient, who should have carried the mutation. In
the remaining two families with uninformative polymorphic DNA markers, the
carrier and noncarrier statuses of four female members could only be deter
mined by direct mutation analysis. Therefore, direct mutation analysis coul
d circumvent the limitations of linkage analysis in the determination of ha
emophilia A carrier status in families without a previous history or inform
ative polymorphic markers.