Hemophilia B: diagnostic value of RFLP analysis in 19 of the 20 known Finnish families.

With the aim of determining the usefulness of RFLP analysis in carrier detection and prenatal diagnosis, we studied all available members including 40 patients, 30 obligate carriers and 39 women at risk belonging to 19 out of a total of 20 Finnish hemophilia B families. The allele frequencies of the three intragenic polymorphisms studied (TaqI, XmnI and DdeI) did not differ significantly from those reported in other Caucasian populations. A considerable degree of linkage disequilibrium between the three polymorphisms was observed. Carriership evaluated in 39 females at risk led to exclusion in 14 while carriership was established in 5. The proportion of women who by pedigree analysis had a carriership risk between 10% and 90% could be reduced from 97% to 51% by RFLP analysis. Prenatal diagnosis using an intragenic polymorphism could potentially be offered to 69% of hemophilia carriers. DNAs from 19 unrelated patients were screened for mutations using a full-length cDNA probe, but no abnormal hybridization patterns were observed. Our results indicate that RFLP segregation analysis provides a useful method of carrier detection and prenatal diagnosis in hemophilia B.