[Educational symposium: DNA diagnosis of malignancies; strategies and applications of PCR-mediated DNA diagnosis in a case of hemophilia B].

Advances in molecular biology have improved the screening of carriers and allows 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 Japanese and other populations. We identified two novel dinucleotide polymorphisms in intron A at nucleotide 192 (FIX192) and in the 5' flanking region at nucleotide-793 (FIX-793) of the factor IX gene, which are present in normal Japanese. The Hha I restriction fragment length polymorphism (FIXHhaI) located 8 kb 3' to the factor IX gene was also found to be an efficient marker for detecting carriers in a Japanese family with hemophilia B. Each of these polymorphisms was able to be rapidly ascertained by the polymerase chain reaction (PCR) technique. In 23 Japanese families with hemophilia B, 19 families (82.6%) were heterozygous for at least one of these polymorphisms. Carrier detection and, possibly, prenatal diagnosis of hemophilia B can be achieved effectively and rapidly in Japanese with these polymorphisms. These polymorphisms may also be present and useful for hemophilia B carrier detection in other Asian populations.