Editor—Phenotypic expression of X linked disorders in females may be the result of an X chromosome anomaly or homozygosity for the mutated gene, but is probably most frequently the result of skewed X chromosome inactivation. Skewed X inactivation may be the result of a chance event, but may also be because of genetic factors.1 We report here the results of X inactivation analysis in a family with haemophilia B, which showed extremely skewed X inactivation both in a female haemophilia patient and in her non-carrier daughter, indicating a possible genetic influence on X chromosome inactivation in this family. Familial skewed X inactivation may interfere with carrier detection, since skewed X inactivation with the mutant gene on the inactive X chromosome may lead to a normal phenotype in a carrier.

The patient was a 40 year old female who belonged to a family with moderate haemophilia B2 (fig 1). Plasma factor IX (FIX) activity was 0.02-0.03 units/ml, which was identical to the FIX activity in the affected male relatives. She had suffered from bleeding episodes after tooth extraction as a child and heavy bleeding from the episiotomy after her first delivery. A C→T transition, causing mutation S360L in exon 8 of the factor IX gene, was found in the male …