Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders

Journal of Thrombosis and Haemostasis : JTH
Bin Zhang, David Ginsburg

Abstract

Combined deficiency of factor (F)V and FVIII (F5F8D) and combined deficiency of vitamin K-dependent clotting factors (VKCFD) comprise the vast majority of reported cases of familial multiple coagulation factor deficiencies. Recently, significant progress has been made in understanding the molecular mechanisms underlying these disorders. F5F8D is caused by mutations in two different genes (LMAN1 and MCFD2) that encode components of a stable protein complex. This complex is localized to the secretory pathway of the cell and likely functions in transporting newly synthesized FV and FVIII, and perhaps other proteins, from the ER to the Golgi. VKCFD is either caused by mutations in the gamma-carboxylase gene or in a recently identified gene encoding the vitamin K epoxide reductase. These two proteins are essential components of the vitamin K dependent carboxylation reaction. Deficiency in either protein leads to under-carboxylation and reduced activities of all the vitamin K-dependent coagulation factors, as well as several other proteins. The multiple coagulation factor deficiencies provide a notable example of important basic biological insight gained through the study of rare human diseases.

References

Mar 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·S M WuD W Stafford
Aug 1, 1990·British Journal of Haematology·B BrennerU Seligsohn
Jul 1, 1989·Physiological Reviews·P V HauschkaC M Gundberg
Nov 1, 1987·The Journal of Cell Biology·J SarasteM G Farquhar
Aug 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·D L DiuguidB Furie
Nov 1, 1985·The Journal of Clinical Investigation·R Wallin, L F Martin
Feb 1, 1985·The Journal of Clinical Investigation·H C ChiuR W Colman
Mar 15, 1974·Biochemical Pharmacology·A Zimmermann, J T Matschiner
Jun 9, 1966·The New England Journal of Medicine·C W McMillan, H R Roberts
Apr 1, 1984·British Journal of Haematology·D A KellyE G Tuddenham
Jan 1, 1980·Acta Haematologica·S J Machin, B R Miller
Nov 4, 1982·The New England Journal of Medicine·U SeligsohnE Zwang
Jan 1, 1980·The American Journal of Medicine·J G HallK M Wilson
Jun 1, 1982·The Journal of Clinical Investigation·G H GoldsmithB Furie
Mar 15, 1996·Science·R Schekman, L Orci
Aug 1, 1996·Nature·P DucyG Karsenty
Feb 15, 1997·The Journal of Clinical Investigation·W C NicholsD Ginsburg
May 5, 1997·The Journal of Cell Biology·E J TisdaleW E Balch
Oct 28, 1996·American Journal of Medical Genetics·A Boneh, J Bar-Ziv
Aug 19, 1997·Proceedings of the National Academy of Sciences of the United States of America·J D KulmanE W Davie
Sep 5, 1997·American Journal of Medical Genetics·A M HoweW S Webster
Apr 8, 1998·British Journal of Haematology·F PeyvandiP M Mannucci

❮ Previous
Next ❯

Citations

Sep 13, 2008·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Qila SaJane L Hoover-Plow
Jun 3, 2005·Nature Reviews. Genetics·Jochen GrawRainer Schwaab
Sep 22, 2005·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Jina BhattacharyyaRenu Saxena
Aug 8, 2008·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Vytautas IvaskeviciusJohannes Oldenburg
Sep 29, 2009·Journal of Veterinary Internal Medicine·B C McGorumA E Thomas
Mar 1, 2007·Blood·Aihua ZhuDavid Ginsburg
Oct 15, 2009·Clinical Chemistry and Laboratory Medicine : CCLM·Massimo Franchini, Pier Mannuccio Mannucci
Mar 4, 2006·International Journal of Hematology·Johannes Oldenburg, Osman El-Maarri
Mar 6, 2016·Annales de dermatologie et de vénéréologie·L GusdorfB Cribier
Aug 12, 2009·Clinics in Laboratory Medicine·Valerie L Ng
Sep 19, 2008·The Journal of Investigative Dermatology·Qiaoli LiJouni Uitto
Jul 2, 2008·Journal of Molecular Biology·Jodie E GuyYlva Lindqvist
Feb 1, 2008·Thrombosis Research·Rocío González-ConejeroVicente Vicente
Mar 11, 2008·Molecular Aspects of Medicine·Enrico Di Cera
Jul 10, 2007·Trends in Biochemical Sciences·Andrea C Baines, Bin Zhang
May 15, 2009·British Journal of Haematology·Connie DuckersElisabetta Castoldi
Jan 15, 2009·Haemophilia : the Official Journal of the World Federation of Hemophilia·B W Weston, P E Monahan
May 13, 2006·Journal of Thrombosis and Haemostasis : JTH·U Seligsohn, D Ginsburg
Jan 20, 2009·Haemophilia : the Official Journal of the World Federation of Hemophilia·P J Robson, A D Mumford
Mar 5, 2008·Journal of Thrombosis and Haemostasis : JTH·G MarchettiF Bernardi
Jan 25, 2006·Insect Biochemistry and Molecular Biology·José M C RibeiroStephen K Wikel
Jan 16, 2009·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Mario LapecorellaGuglielmo Mariani
Jan 24, 2006·The Journal of Biological Chemistry·Leslie A BushEnrico Di Cera
Apr 13, 2007·The Journal of Biological Chemistry·Francesca MarinoEnrico Di Cera
May 8, 2009·Biological & Pharmaceutical Bulletin·Kazuo Yamamoto
Nov 30, 2016·Hematology·Akbar DorgalalehMorteza Shamsizadeh

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.