Framework-dependent in vivo expression of two missense mutations (pro¹²³-->thr and ala²⁴⁴-->val) in the coagulation factor vii gene from a Maltese kindred

Abstract

Coagulation factor VII (CFVII) is a trace vitamin K-dependent plasma glycoprotein (1) which, subsequent to activation, plays a pivotal role in the initiation of blood coagulation. Hereditary CFVII deficiency (2) is a rare coagulopathy, inherited in an autosomal recessive manner with high penetrance and variable expression (3). On the other hand, increased CFVII coagulant activity has been identified as a risk factor for ischaemic heart disease (4)·. Traditionally, CFVII functional variants have been described on the basis of diverse activation patterns of the extrinsic pathway when thromboplastins from brains of different mammalian species are employed in the clotting assay (5-7). In the last few years, 24 gene mutations have been reported. In this report, we describe two additional molecular variants which were identified in a Maltese kindred with hereditary CFVII deficiency, and, established partial haplotypes which could account for the diversity in levels of activity both among wild-type and mutant CFVII proteins.