title: Molecular and clinical aspects of factor VII deficiency.
abstract: Factor VII (FVII) plays an important role in the initiation of blood coagulation, forming a complex with tissue factor (TF) which activates FIX and FX and FVII zymogen. FVII deficiency displays considerable phenotypic and molecular heterogeneity and there are inconsistencies between the clinical picture observed and the underlying clotting and molecular defects. We have reviewed the data available in the literature on FVII-deficient patients. Clinically, cases range from asymptomatic to patients with severe haemorrhagic tendencies. Asymptomatic patients typically have FVII activity levels of >20% and are heterozygotes, double heterozygotes or homozygotes. Mild FVII-deficient patients, with FVII activity levels >2%, may be double heterozygotes or homozygotes for FVII gene missense mutations. Undetectable FVII levels in severely affected patients are often due to severe gene defects such as frameshifts or mutations affecting the splice sites. The analysis of structure-function relationships in FVII deficiency is difficult due to the complexity of the interactions involving FVII. Also, assays using different reagents may give different results with a given plasma sample, and are not very accurate at low levels of FVII which, although relatively low, may be clinically significant, adding complexity to the analysis of FVII deficiency. The sensitivity of our methods for phenotypic evaluation of FVII deficiency remains inadequate.
authors.affiliation: Haematology and Bone Marrow Transplantation Unit, University of Palermo Medical School, Italy. mariangu@tin.it
authors.forename: G
authors.initials: G
authors.lastname: Mariani
authors.forename: L
authors.initials: L
authors.lastname: Lo Coco
authors.forename: F
authors.initials: F
authors.lastname: Bernardi
authors.forename: M
authors.initials: M
authors.lastname: Pinotti
mesh_terms: D005168:Factor VII Deficiency / Q000151:congenital / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D020125:Mutation, Missense; D010641:Phenotype; D013329:Structure-Activity Relationship