Rapid Detection of the Fibrinogen Aα16Arg→His Mutation

Abstract

We have now identified mutations in 17 families with dysfibrinogenemias. Over half of these families have the Aα16Arg→His mutation. This mutation is the most commonly reported cause of dysfibrinogenemia and, like other dysfibrinogenemias, is readily detected because of the associated prolonged thrombin and reptilase times (1)(2)(3). The mutation alters the thrombin cleavage site such that release of fibrinopeptide A is delayed. However, fibrinopeptide release assays are difficult and do not directly confirm the molecular basis of the impaired fibrinopeptide release. We have therefore designed a rapid and technically simple PCR-based method for detection of the Aα16Arg→His mutation. This allows reliable identification of a common dysfibrinogenemia that, in its heterozygous form, is usually asymptomatic and does not pose any substantial threat to the health of the patient. Application of this method will allow clinical laboratories to determine the molecular defect in many of the cases that they detect during coagulation studies. We examined nine families with the Aα16Arg→His mutation. These had been referred for further investigation when routine coagulation studies were consistent with dysfibrinogenemia. All procedures were carried out in accordance with the guidelines of our local ethics committee. Blood samples were collected into Na+ citrate Vacutainer Tubes (Becton Dickinson), and coagulation studies were performed by routine clinical tests for thrombin and reptilase times. …