title: Methylation analysis of the promoter region and intron 1 of the factor VIII gene in haemophilia A patients.
abstract: Methylation, CpG island, promoter, intron 1 Haemophilia A is the most common X-linked inherited coagulation disorder caused by a deficiency of the factor VIII protein (FVIII). A plethora of different mutations in the factor VIII gene (F8) have been identified as causative for this bleeding disease including a few promoter mutations. However, in approximately 2-5% of all haemophilic patients, the causal mutation still remains unknown. To our knowledge, epigenetic abnormalities in regulatory regions of the F8 gene have not yet been implicated in the disease pathogenesis. We therefore developed bisulfite pyrosequencing assays to screen patients with unknown mutation status for their methylation patterns in presumed regulative regions of the F8 gene (5'UTR and intron 1). The methylation patterns of haemophilia A patients did not differ from that of controls. In three patients, chromosomal aberrations were identified which could be associated with a defective FVIII synthesis.
authors.affiliation: Melanie Andrea Zimmermann, Department of Human Genetics, University of Würzburg, Biocenter, Am Hubland, 97074 Würzburg, Germany, Tel. +49/(0)931/318 12 78; Fax +49/(0)931/318 40 69, E-mail: melanie.zimmermann@uni-wuerzburg.de.
authors.forename: M A
authors.initials: MA
authors.lastname: Zimmermann
authors.forename: T
authors.initials: T
authors.lastname: Hansmann
authors.forename: T
authors.initials: T
authors.lastname: Haaf
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.forename: C R
authors.initials: CR
authors.lastname: Müller
authors.forename: S
authors.initials: S
authors.lastname: Rost
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D019175:DNA Methylation / Q000235:genetics; D005169:Factor VIII / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D005858:Germany / Q000453:epidemiology; D006467:Hemophilia A / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015994:Incidence; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D005169:Factor VIII