Advances in molecular biology have improved the screening for carriers and the prenatal diagnosis of many genetic disorders, including hemophilia B. For instance, based on the eight described dimorphic restriction fragment length polymorphisms within the factor IX gene, a Caucasian female has a 94% chance of being heterozygous (informative) for at least one of these markers. However, ethnic limitations of molecular genetic techniques have been found in diagnosing hemophilia B families in the Japanese and other populations. Previously, we heve demonstrated that three dinucleotide polymorphisms, which locate in the 5' flanking region at nucleotide-793 (FIX-793), in intron A at nucleotide 192 (FIX192), and in the 3' flanking region (FIXHhaI), of the factor IX gene, are present in normal Japanese. Each of these polymorphisms was able to be rapidly ascertained by the polymerase chain reaction technique.
In this study, we analyzed 23 Japanese families with hemophilia B, and found that 19 families (82.6%) were heterozygous for at least one of these polymorphisms. Using these polymorphisms together with the extragenic DXS99/Sac I PFLP, which was previously reported as a useful gene marker for Japanese hemophilia B, the informative rate impproved to 87.0%. Carrier detection and the prenatal diagnosis of hemophilia B can be achieved effectively and rapidly in Japanese with these polymorphisms. In fact, we have successfully performed the prenatal diagnosis in two Japanese families with hemophilia B by using FIXHhaI or FIX192 polymorphism analysis. These polymorphisms may also be present and useful for hemophilia B carrier detection in other Oriental population.
