A past mutation at Isoleucine397 is now a common cause of moderate/mild haemophilia B

Cynthia D.K. Bottema, Dwight D. Koeberl, Rhett P. Ketterling, E. J.W. Bowie, Sherryl A.M. Taylor, David Lillicrap, Amy Shapiro, Gerald Gilchrist, Steve S. Sommer

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Of the factor IX sequence changes that we have identified in 65 consecutive males with haemophilia B, 11 (17%) are the same mutation. This mutation is a T→C transition at base 31311 which substitutes threonine for isoleucine397 (ile397) in the factor IX molecule. The 11 patients are of Western European descent and have the same haplotype: Hinf1 (‐), Xmn1 (‐), Taq1 (‐), BamH1 (+), Malmö allele = thr148. The frequency of this haplotype was estimated and the probability of the same mutation occurring independently 11 times in this haplotype was miniscule. We conclude that these patients have a common ancestor despite the lack of overlapping pedigrees. The clinical symptoms of the disease were consistently moderate/mild in these 11 patients, whereas factor IX coagulation values obtained from the medical records varied more than sixfold between individuals. However, when plasma from five individuals was assayed by the same laboratory concurrently, the values varied less than twofold. Thus, in routine practice, clinical severity may correlate better with the presence of a given mutation than the factor IX coagulant activity. The high frequency of the mutation at ile397 indicates that carrier testing in families of Northern European descent with moderate/mild haemophilia B can be expedited by first determining whether this particular mutation is present. We demonstrate here that the technique of polymerase chain reaction (PCR) amplification of specific alleles (PASA) can be used to rapidly perform carrier testing in families with the ile397 mutation.

Original languageEnglish (US)
Pages (from-to)212-216
Number of pages5
JournalBritish journal of haematology
Issue number2
StatePublished - Jun 1990

ASJC Scopus subject areas

  • Hematology


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