Interaction of incontinentia pigmenti and factor VIII mutations in a female with biased X inactivation, resulting in haemophilia.
We report a female infant born to a mother with incontinentia pigmenti (IP) and a father with haemophilia A, who manifests both disorders. Analysis of peripheral blood DNA from the infant, her mother, and two female relatives with IP showed a highly skewed pattern of X inactivation. Random patterns were observed in the infant's two sisters, who do not have IP and have normal carrier activity of factor VIII. Preferential inactivation of the X chromosome bearing the IP mutation, probably by negative selection, appears to have unmasked the factor VIII mutation on the infant's other X chromosome. This illustrates an unusual mechanism for the manifestation of an X linked disease in a heterozygous female.
Coleman
R
R
Department of Dermatology, Hospitals for Sick Children, London, UK.
Genet
S A
SA
Harper
J I
JI
Wilkie
A O
AO
D004303:Dosage Compensation, Genetic; D005169:Factor VIII / Q000235:genetics; D005192:Family Health; D005260:Female; D006580:Genetic Carrier Screening; D006467:Hemophilia A / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007184:Incontinentia Pigmenti / Q000150:complications / Q000235:genetics*; D007223:Infant; D010375:Pedigree
D005169:Factor VIII