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   identification and characterization of a novel variant in c-terminal region of antithrombin (ala427thr) associated with type ii at deficiency leading to polymer formation  
   
نویسنده bhakuni teena ,sharma amit ,biswas arijit ,bano shadabi ,mahapatra manoranjan ,saxena renu ,jairajpuri mohamad aman
منبع journal of thrombosis and thrombolysis - 2020 - دوره : 50 - شماره : 3 - صفحه:678 -685
چکیده    Antithrombin (at) deficiency is a rare but strong risk factor for the thrombosis development. mutations in gene encoding at (serpinc1) have provided a detailed understanding of at deficiency and subsequent development of thrombotic complications. in the present study, we describe a case of thrombotic patient with reduced at activity and normal at antigen levels. at deficiency in the patient was explained by the presence of heterozygous mutation g.13397a>g (ala427thr) in exon 6 of serpinc1. reduced aptt and tt with normal pt were observed. the mutation was found to be absent in healthy controls (n = 62). in vitro purification and characterization of variant at showed significant decrease in fluorescence emission intensity, decreased bis-ans fluorescence emission, changes in secondary structure and presence of polymerized at in patient’s plasma as assessed by fluorescence, circular dichroism and transmission electron microscopy respectively. furthermore, molecular dynamics simulation studies showed altered conformation due to ala427thr substitution. our study shows that genetic screening should be carried out in at deficient patients in addition to the routinely used functional assays to understand the molecular basis of disease development.
کلیدواژه antithrombin ,molecular dynamics simulation ,mutations ,polymerization ,thrombosis
آدرس protein conformation and enzymology lab, department of biosciences, india, all india institute of medical sciences, department of hematology, india, university clinic bonn, institute of experimental haematology and transfusion medicine, germany, protein conformation and enzymology lab, department of biosciences, india, all india institute of medical sciences, department of hematology, india, all india institute of medical sciences, department of hematology, india, protein conformation and enzymology lab, department of biosciences, india
 
     
   
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