Hereditary coagulation factor VII deficiency caused by novel compound heterozygous mutations c.572-1G>A and c.1037A>C in a Chinese pedigree.

ABSTRACT

Hereditary coagulation factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder. The aims of this study were to identify and verify the pathogenic mutation sites in a family with hereditary coagulation FVII deficiency, and preliminarily explore the underlying mechanisms. We identified a novel combination of compound heterozygous mutations, c.572-1G>A and c.1037A>C in F7 gene, associated with FVII deficiency. The splice site mutation c.572-1G>A led to a truncation, resulting in the loss of the essential catalytic domain of the FVII protein. The c.1037A>C missense mutation has not been previously reported. Our study revealed that this mutation leads to steric hindrance between residues, causing significant changes in the energy and structure of the FVII protein, ultimately affecting its function. These changes disrupt the normal function of the FVII protein, accelerating the development of inherited FVII deficiency. Moreover, the mRNA expression of the F7 gene and the protein expression of the FVII antigen (FVII Ag) were significantly lower in the proband, as well as in the proband's parents, compared to the healthy control (P<0.05). Our findings not only elucidate the genetic underpinning of FVII deficiency in the family studied but also contribute a new mutation to the known disease spectrum, potentially assisting in future diagnostic and therapeutic approaches.