title: Absence of correlation between X chromosome inactivation pattern and plasma concentration of factor VIII and factor IX in carriers of haemophilia A and B.
abstract: Haemophilia A and B are X-linked disorders which are due to a reduced activity of coagulation factor VIII or IX, respectively. Female carriers have a wide range of plasma concentration of factor VIII or factor IX, and may in rare cases have an affected phenotype. In order to investigate if this variation is related to X chromosome inactivation, we determined the X inactivation pattern in 31 haemophilia A and 15 haemophilia B carriers, using a PCR in the androgen receptor locus in blood DNA. Seven of the haemophilia A carriers and none of the haemophilia B carriers had a skewed pattern (> or =80:20). One of the skewed haemophilia A carriers had a low plasma concentration of factor VIII (0.15 U/ml), but the remaining 6 carriers did not differ in factor VIII concentration from that of carriers with a random X inactivation pattern. One carrier with a high factor VIII concentration (2.0 U/ml) did not have a skewed pattern. Similarly, for the haemophilia B carriers, there was no tendency to a more skewed X inactivation pattern in the carriers with low or high factor IX concentrations. In addition, we analysed a female with haemophilia B who was heterozygous for the mutation R180W in the factor IX gene. She had a random X chromosome inactivation pattern. We conclude that the wide range in plasma concentration of factor VIII and factor IX in haemophilia A and B carriers cannot in general be explained by the X chromosome inactivation pattern in peripheral blood cells.
authors.affiliation: Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway. k.h.orstavik@ioks.uio.no
authors.forename: K H
authors.initials: KH
authors.lastname: Orstavik
authors.forename: E
authors.initials: E
authors.lastname: Scheibel
authors.forename: J
authors.initials: J
authors.lastname: Ingerslev
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004303:Dosage Compensation, Genetic; D005164:Factor IX / Q000235:genetics / Q000378:metabolism*; D005169:Factor VIII / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006239:Haplotypes; D006467:Hemophilia A / Q000097:blood* / Q000235:genetics*; D002836:Hemophilia B / Q000097:blood* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation
chemical_list: D005169:Factor VIII; D005164:Factor IX