Haemophilia B carrier detection by factor IX:C analysis; no impact of the type of mutation or severity of disorder.

Abstract

Haemophilia B, an X-linked recessive bleeding disorder characterized by lack or deficiency of factor IX, has been shown to be caused by any of a variety of DNA abnormalities (partial or total deletions, nonsense or missense mutations). Since in most countries carrier detection is based on factor IX coagulant activity (FIX:C) assay, this study was designed to determine whether carriers' FIX:C values are dependent on the severity of haemophilia (mild, moderate or severe) or on the genetic anomaly in the family. FIX:C concentrations were studied in 28 obligate carriers, 39 women known to carry the mutation and 33 verified noncarriers subgrouped by severity of disorder or genetic anomaly. No significant subgroup differences in FIX:C values were found, thus suggesting the level of FIX:C concentrations in carriers to be unaffected by the severity of haemophilia, or by its expression (i.e. deficient or dysfunctional factor IX). The specificity and sensitivity of FIX:C analysis for the purpose of carrier diagnosis was judged by receiver operating characteristic curve analysis, where an FIX:C cut-off level of 75 IU dL-1 was found to be optimal (sensitivity 93% and specificity 88%).