title: Molecular diagnostics of 15 hemophilia A patients: characterization of eight novel mutations in the factor VIII gene, two of which result in exon skipping.
abstract: The X-linked bleeding disorder hemophilia A is caused by mutations in the coagulation factor VIII gene. A high frequency of de novo mutations and the large size of this gene complicate the molecular diagnostic of hemophilia A. Characterization of mutations, however, may help identify amino acids or regions with essential functional or structural properties and thereby clarify the mechanism of pathogenesis. In the present study, we describe the identification of 15 mutations in the factor VIII gene, of which eight are novel. Among the patients with severe hemophilia A, two splice mutations (IVS5-3 and IVS19-2), a 4-bp deletion ((TACA) at codon 1215, and a missense mutation G1850V have been characterized. The missense mutations G479R, R531C, V537D, N2129S and I2190N were found for five patients with a moderate course of hemophilia A disease. A silent mutation resulting in activation of a cryptic acceptor splice site within exon 11 and four other missense mutations Y114C, R1689H, R2150H (2x), M2164V have been identified for six patients with mild hemophilia A.
authors.affiliation: Institut für Humangenetik der Westfälischen Wilhelms-Universität Münster, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Tavassoli
authors.forename: A
authors.initials: A
authors.lastname: Eigel
authors.forename: K
authors.initials: K
authors.lastname: Wilke
authors.forename: H
authors.initials: H
authors.lastname: Pollmann
authors.forename: J
authors.initials: J
authors.lastname: Horst
mesh_terms: D000818:Animals; D002570:Ceruloplasmin / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005169:Factor VIII / Q000235:genetics*; D006467:Hemophilia A / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D051379:Mice; D009154:Mutation; D020125:Mutation, Missense; D012326:RNA Splicing / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D005169:Factor VIII; D002570:Ceruloplasmin