Scientists have made further discoveries into the genetics of antithrombin deficiency, which places some individuals at a raised risk of clotting disorders.
Hereditary deficiency in antithrombin affects about one in two thousand people. It was investigated by Dr Irene Martinez-Martinez and her team at the Universidad de Murcia in Spain.
They discovered two mutations, called S365L and I207T, in people with type II antithrombin deficiency, and showed that they prevent normal antithrombin activity towards the end of the antithrombin-creation pathway.
In The Journal of Biological Chemistry they write that these mutations 'cause significant impairment of antithrombin function, mainly increasing inhibition. Essentially, such mutations point out a new functional domain in which natural mutations might have clinical relevance for antithrombin.'
Dr Martinez-Martinez comments: 'We saw that we had mutants that were affecting the function of the protein even though they were very far from the main part of the protein that is in charge of the inhibition.
'People thought that the antithrombin function was mainly focused on one domain of the protein. With this work, we have realised that is not true.'
The team hope that this new understanding of the importance of this region of the antithrombin protein could lead to improved treatments for patients with antithrombin deficiency, and other blood disorders.
They add that the true nature of this domain could not have been predicted from simply studying the sequences of healthy antithrombins.
'This work has been possible thanks to the characterisation of mutations identified in patients,' Dr Martinez-Martinez states.
Source: Aguila, S. et al. Disease-causing mutations in the serpin antithrombin reveal a key domain critical for inhibiting protease activities. Journal of Biological Chemistry 25 July 2017; doi: 10.1074/jbc.M117.787325
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