Recent developments in the understanding of the combined deficiency of FV and FVIII.

ABSTRACT: Combined deficiency of factor V (FV) and factor VIII (FVIII) (F5F8D) is a genetic disorder characterized by mild-to-moderate bleeding and coordinate reduction in plasma FV and FVIII levels, as well as platelet FV level. Recent studies identified mutations in two genes (LMAN1 and MCFD2) as the cause of F5F8D. Though clinically indistinguishable, MCFD2 mutations generally exhibit lower levels of FV and FVIII than LMAN1 mutations. LMAN1 is a mannose-specific lectin that cycles between the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment. MCFD2 is an EF-hand domain protein that forms a calcium-dependent heteromeric complex with LMAN1 in cells. Missense mutations in the EF-hand domains of MCFD2 abolish the interaction with LMAN1. The LMAN1-MCFD2 complex may serve as a cargo

SUBMITTER: Zhang B 

PROVIDER: S-EPMC2777536 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature