title: Direct mutation analysis as the preferred method for carrier diagnosis in families with isolated cases of haemophilia B.
abstract: Approximately one-third of haemophilia B cases are described as isolated due to their occurrence in families with no prior history of the disorder. In this report, two families with isolated haemophilia B were studied by the standard method of restriction fragment length polymorphism (RFLP) analysis coupled with factor IX activity and antigen levels with the aim of achieving carrier diagnoses. The limitations of using this approach in the determination of carrier status were highlighted by diagnostic problems arising in both families. The problems included difficulty in interpreting bioassay results, homozygosity for the RFLP marker in a key family member and the possibility of germline mosaicism. Unequivocal carrier diagnosis in the two families was ultimately achieved by direct mutation analysis.
authors.affiliation: Molecular Pathology Unit, Institute of Medical and Veterinary Science, Adelaide, South Australia.
authors.forename: A E
authors.initials: AE
authors.lastname: Andrews
authors.affiliation: Molecular Pathology Unit, Institute of Medical and Veterinary Science, Adelaide, South Australia.
authors.forename: G J
authors.initials: GJ
authors.lastname: Casey
authors.affiliation: Molecular Pathology Unit, Institute of Medical and Veterinary Science, Adelaide, South Australia.
authors.forename: S E
authors.initials: SE
authors.lastname: Rodgers
authors.affiliation: Molecular Pathology Unit, Institute of Medical and Veterinary Science, Adelaide, South Australia.
authors.forename: R L
authors.initials: RL
authors.lastname: Flower
authors.affiliation: Molecular Pathology Unit, Institute of Medical and Veterinary Science, Adelaide, South Australia.
authors.forename: Z
authors.initials: Z
authors.lastname: Rudzki
keywords: RFLP; amplification mismatch detection; carrier diagnosis; chemical cleavage; haemophilia B; isolated