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, Table of Contents

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

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

› Author Affiliations

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.

Full Text

References

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