title: Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees.
abstract: The molecular defects causing severe factor IX deficiency were identified in two distinct canine breed-variants. Both defects were associated with an absence of plasma factor IX coagulant activity and antigen. A large deletion mutation was found in 1 breed variant, spanning the entire 5' region of the factor IX gene extending to exon 6. An approximately 5 kb insertion disrupted exon 8 of the second breed-variant. This insertion was associated with alternative splicing between a donor site 5' and acceptor site 3' to the normal exon 8 splice junction, with introduction of a new stop codon. The resultant transcript lacked most of the factor IX catalytic domain and 3' untranslated region. Molecular analyses of canine hemophilia B define an experimental model for study of inhibitor formation and gene therapy strategies, and provide insight into spontaneous mutation mechanisms in the factor IX gene and on the X chromosome of mammalian species.
authors.affiliation: James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: W
authors.initials: W
authors.lastname: Gu
authors.forename: M
authors.initials: M
authors.lastname: Brooks
authors.forename: J
authors.initials: J
authors.lastname: Catalfamo
authors.forename: J
authors.initials: J
authors.lastname: Ray
authors.forename: K
authors.initials: K
authors.lastname: Ray
mesh_terms: D000818:Animals; D001483:Base Sequence; D004285:Dogs; D005164:Factor IX / Q000235:genetics*; D005260:Female; D002836:Hemophilia B / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: D005164:Factor IX