title: Severe haemophilia A in a female: a compound heterozygote with nonrandom X-inactivation.
abstract: We report a case of severe haemophilia A (<1% factor VIII level) in a female resulting from an interesting and improbable combination of events. The patient inherited a factor VIII intron 22 inversion from her carrier mother, as well as a second factor VIII inversion involving intron 22 that arose de novo on her paternally derived X chromosome. In addition, the patient's paternally derived X chromosome had been preferentially inactivated in 95+% of her somatic cells. The patient's mother, who was clinically unaffected, carried an intron 22 inversion as well and also showed nonrandom X-inactivation. The patient's mother had a brother with severe haemophilia A. It is therefore likely that the mother's inversion was on her maternally derived X chromosome. Since she was unaffected, it is likely that her inversion-bearing X was the one that was preferentially inactivated.
authors.affiliation: Department of Paediatrics, Michael Reese Hospital and University of Illinois, Chicago, Illinois, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Seeler
authors.forename: C L
authors.initials: CL
authors.lastname: Vnencak-Jones
authors.forename: L M
authors.initials: LM
authors.lastname: Bassett
authors.forename: J B
authors.initials: JB
authors.lastname: Gilbert
authors.forename: R C
authors.initials: RC
authors.lastname: Michaelis
mesh_terms: D015139:Blotting, Southern; D007446:Chromosome Inversion; D019175:DNA Methylation; D005169:Factor VIII / Q000235:genetics; D005192:Family Health; D005260:Female; D020868:Gene Silencing; D006467:Hemophilia A / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics
chemical_list: D005169:Factor VIII