title: Lack of F8 mRNA: a novel mechanism leading to hemophilia A.
abstract: Hemophilia A (HA) is caused by partial or total deficiency of F8 protein activity. In a small group, about 1.8% of patients with HA, no mutation is found in the F8 gene. Among this group, we report here on one patient with severe HA in whom no mRNA of the F8 gene was detected. Using 2 common polymorphisms in F8 exon 14, we were able to show that the same allele shared by the patient, his mother, and his sister was not detected by reverse transcription-polymerase chain reaction (RT-PCR) from total blood mRNA. Skewed X-chromosome inactivation in both the mother and the sister was excluded by studying the methylation profile of the androgen receptor gene (HUMARA locus). These findings strongly suggest that the cause of HA in this patient is either absence or rapid degradation of the F8 mRNA, which points to a novel mechanism leading to HA.
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, Sigmund Freud Str 25, 53127 Bonn, Germany. Osman.Elmaarri@ukb.uni-bonn.de
authors.forename: Osman
authors.initials: O
authors.lastname: El-Maarri
authors.forename: Heike
authors.initials: H
authors.lastname: Singer
authors.forename: Claudia
authors.initials: C
authors.lastname: Klein
authors.forename: Matthias
authors.initials: M
authors.lastname: Watzka
authors.forename: Ursula
authors.initials: U
authors.lastname: Herbiniaux
authors.forename: Hans H
authors.initials: HH
authors.lastname: Brackmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Schröder
authors.forename: Jochen
authors.initials: J
authors.lastname: Graw
authors.forename: Clemens R
authors.initials: CR
authors.lastname: Müller
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schramm
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwaab
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
authors.forename: Peter
authors.initials: P
authors.lastname: Hanfland
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
mesh_terms: D000293:Adolescent; D019175:DNA Methylation; D005169:Factor VIII / Q000235:genetics*; D005190:Family; D005260:Female; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D011944:Receptors, Androgen; C078147:F8 protein, human; D005169:Factor VIII