Interaction of incontinentia pigmenti and factor VIII mutations in a female with biased X inactivation, resulting in haemophilia.

Abstract

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.

• Authors: R Coleman, S A Genet, J I Harper, A O Wilkie
• Journal: Journal of medical genetics (J Med Genet) Vol. 30 Issue 6 Pg. 497-500 (Jun 1993) ISSN: 0022-2593 [Print] England
• PMID: 8326493 (Publication Type: Case Reports, Journal Article)

Chemical References

• Factor VIII

Topics

• Dosage Compensation, Genetic
• Factor VIII (genetics)
• Family Health
• Female
• Genetic Carrier Screening
• Hemophilia A (complications, genetics)
• Heterozygote
• Humans
• Incontinentia Pigmenti (complications, genetics)
• Infant
• Pedigree