By Owen P Smith; Ian M Hann
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Extra info for Essential paediatric haematology
Consequently, the FII variant (G20210A) is a risk factor for VTE second only to factor V Leiden. FII is the circulating precursor of the serine protease thrombin, a key enzyme in the processes of haemostasis and thrombosis, which exhibits procoagulant, anticoagulant and antifibrinolytic activities. G20210A is associated with elevated FII levels; thus carriers of this allele have significantly higher FII levels than non-carriers, suggesting that G20210A acts through the elevated FII levels. Studies in families presenting with VTE indicated that the presence of more than one mutation (FVL, G20210A) with or without the presence of environmental factors may increase the risk of thrombotic disease, and many thrombosis clinics now perform genetic testing for these two variants.
But what of molecular therapeutics? Somatic gene therapy has been the goal of many scientists and clinicians for the last 10 years. What is the progress to date? Somatic gene therapy involves the amelioration of a disease by introduction of genetic material with therapeutic potential into a somatic tissue. It is only in the last 5–10 years that gene transfer could be contemplated in the clinic. Gene therapy has benefited from (i) the gene transfer and expression techniques of molecular genetics, (ii) the natural ability of retroviruses to infect foreign replicating cells and stably integrate their genetic material into the host genome, and (iii) the fact that SCT provides a straightforward delivery of in vitro manipulated material into the blood stream.
This single point mutation has been termed factor V Leiden (FVL). This particular mutation accounts for 95% of the hereditary forms of activated protein C resistance (APCR). The mutation is a G-to-A transition at position 1691 in exon 10, which leads to a replacement of R at position 506 by Q (glutamine). FVa:Q-506 is not cleaved at position 506 by APC, resulting in a general hyper- coagulation state. FVL is highly prevalent in Caucasian populations: the mean allele frequency throughout Europe has been estimated to be 2–7%, although in Scandinavian populations it may be as high as 12%.