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Severe haemophilia A in a female: a compound heterozygote with nonrandom X‐inactivation
Author(s) -
Seeler Ra,
Vnencak-Jones Cl,
Bassett Lm,
Gilbert Jb,
Michaelis Rc
Publication year - 1999
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1046/j.1365-2516.1999.00352.x
Subject(s) - chromosomal inversion , haemophilia a , heterozygote advantage , intron , x inactivation , x chromosome , compound heterozygosity , haemophilia , genetics , somatic cell , inversion (geology) , chromosome , medicine , genotype , biology , gene , allele , karyotype , paleontology , structural basin
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.