Molecular analysis of factor XII gene in Thai patients with factor XII deficiency

Abstract

Factor XII is the initiating protein of the intrinsic coagulation pathway. It activates factor X after being activated by the so called 'contact system'. Both congenital factor XII deficiency, usually without bleeding symptoms, and several factor XII polymorphisms with possible thrombotic tendency have been described. In the presented work, two Thai patients with congenital factor XII deficiency have been studied by utilizing a PCR single-stranded conformation polymorphism (PCR-SSCP) method followed by direct sequencing. A new mutation of factor XII gene in the exon 7, c.583delC or p.H195fsX250, has been discovered and variable factor activities resulting from different mutations with or without polymorphisms are demonstrated. The other case had a homozygous missense mutation, c.G218C. Heterozygotes of this mutation, found in 1.9% (2/107) of healthy Thai volunteers, showed low factor XII activities suggesting that it is a deleterious mutation.