DIRECT MUTATION ANALYSIS AS THE PREFERRED METHOD FOR CARRIER DIAGNOSIS IN FAMILIES WITH ISOLATED CASES OF HEMOPHILIA-B

Approximately one-third of haemophilia B cases are described as isolat ed due to their occurrence in families with no prior history of the di sorder. In this report, two families with isolated haemophilia B, were studied by the standard method of restriction fragment length polymor phism (RFLP) analysis coupled with factor IX activity and antigen leve ls with the aim of achieving carrier diagnoses. The limitations of usi ng this approach in the determination of carrier status were highlight ed by diagnostic problems arising in both families. The problems inclu ded difficulty in interpreting bioassay results, homozygosity for the RFLP marker in a key family member and the possibility of germline mos aicism. Unequivocal carrier diagnosis in the two families was ultimate ly achieved by direct mutation analysis.