Two Distinct Mutations Cause Severe Hemophilia B in Two Unrelated Canine Pedigrees

Weikuan Gu; Marjory Brooks; James Catalfamo; Jharna Ray; Kunal Ray

doi:10.1055/s-0037-1614374

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1999; 82(04): 1270-1275
DOI: 10.1055/s-0037-1614374

Review Article

Schattauer GmbH

Two Distinct Mutations Cause Severe Hemophilia B in Two Unrelated Canine Pedigrees

Authors

Weikuan Gu²

¹From the James A. Baker Institute for Animal Health and the Comparative Coagulation Section, Diagnostic Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
Marjory Brooks

²Comparative Coagulation Section, Diagnostic Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
James Catalfamo

²Comparative Coagulation Section, Diagnostic Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
Jharna Ray¹

¹From the James A. Baker Institute for Animal Health and the Comparative Coagulation Section, Diagnostic Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
Kunal Ray

¹From the James A. Baker Institute for Animal Health and the Comparative Coagulation Section, Diagnostic Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA

Abstract

Summary

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.

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Referenzen

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