combined deficiency of coagulation factors V and VIII
MIM.227300 18q21.3-q22 and 2p21-p16.3
Saturday 3 June 2006
Combined deficiency of coagulation factors V and VIII is characterized by a moderate bleeding tendency and low plasma concentrations of these two factors.
It is caused by mutations in LMAN1 (ERGIC-53) (MIM.601567), a mannose-binding lectin that cycles between the endoplasmic reticulum and the Golgi apparatus and in MCFD2 (MIM.607788).
Mutations in a sorting receptor that recognizes carbohydrate ligands were characterized as the cause of the combined deficiency of coagulation factors V and VIII.
LMAN1 (ERGIC-53) (MIM.601567) may interact with coat-protein complexes that drive the budding of transport vesicles in the early secretory pathway and may thus be directly involved in the sorting of glycoproteins.
The LMAN1 protein was totally absent in cells of patients who were homozygous for the mutation, leading to defective secretion of the two coagulation factors, which were apparently retained in the endoplasmic reticulum.
However, the patients had normal plasma concentrations of other proteins, suggesting that the function of ERGIC-53 is specific for a subgroup of the glycoproteins that are transported out of the endoplasmic reticulum.
Olkkonen VM, Ikonen E. Genetic defects of intracellular-membrane transport. N Engl J Med. 2000 Oct 12;343(15):1095-104. PMID: #11027745#