ABSTRACT
INTRODUCTION: Dysfibrinogenemia is a rare inherited disease that results from mutation in one of the three fibrinogen genes. Diagnosis can be misleading since it may present as a bleeding tendency or thrombosis and a specific coagulation test for diagnosis is not routinely available. AIM: To search for a new candidate gene of thrombophilia in a family with three generations of arterial and venous thrombosis. METHODS: Whole exome sequencing followed by Sanger validation and segregation analysis was carried out. In addition, structural modeling was performed. Screening for thrombophilia along with blood counts, prothrombin time, activated partial thromboplastin, thrombin, reptilase time, and fibrinogen was done in each patient. RESULTS AND DISCUSSION: A missense c.259A>C, p.K87Q (g.chr4: 155510050A-C) (rs764281241) in FGA gene was found in all three siblings without any other known thrombophilia marker to explain thrombosis in all three siblings. It is expected to be damaging by six out of seven prediction programs and is very rare in the entire population with Exac=0.000008. CONCLUSION: The occurrence of the c.259A>C mutation in FGA may well explain the thrombosis phenotype of the affected family and is suggested as a new marker for thrombophilia phenotype.
