ABSTRACT
Two sisters (III.2 and III.3, as shown below) attend to be screened for haemophilia B. Their brother (III.1) and uncle (II.1) are known to have severe haemophilia B. Genetic analysis of the brother showed complete failure of amplification by polymerase chain reaction (PCR) of all F9 exons indicating that the defect is a deletion of the whole F9 gene. As large deletions cannot be directly detected by conventional sequencing techniques, a linkage analysis is carried out to detect a restriction fragment length polymorphism (RFLP) in intron 3 of F9 that affects cleavage by the restriction endonuclease XmnI. Depending on whether the polymorphism is present or not, the band sizes amplified by PCR are 124 or 163 bp.
