Mutation detection, prenatal testing, and delineation of the germline origin in a family with sporadic hemophilia B and No living hemophiliacs

Hemophilia B is an X-linked recessive disorder affecting 1 in 30,000 males. Determination of carrier status for at risk females can be done by utilizing indirect methods such as RFLP analysis or by direct methods such as DNA sequencing. However, in most cases, reliable carrier testing is not possible without first analyzing the DNA from an affected male in the family to determine his haplotype/causative sequence change. In the case presented here, the only affected male in the family has been deceased for 25 years; no DNA was available from him. The sister (III-2) of the affected individual was a suspected carrier based on her factor IX coagulant (36%); she was pregnant with a male fetus, and requested prenatal testing.