CASE REPORTSA novel frameshift mutation in FGA (c.1846 del A) leading to congenital afibrinogenemia in a consanguineous Syrian familyLevrat, Emmanuela; Aboukhamis, Imadb; de Moerloose, Philippea; Farho, Jaafarb; Chamaa, Saharb; Reber, Guidoa; Fort, Alexandrec; Neerman-Arbez, MargueritecAuthor Information aDivision of Angiology and Haemostasis, University Hospital, Geneva, Switzerland bDamascus University and Arab International University, Damascus, Syria cDepartment of Genetic Medicine and Development, University Medical School Geneva, Geneva, Switzerland Received 9 July, 2010 Revised 18 November, 2010 Accepted 20 November, 2010 Correspondence to Professor Marguerite Neerman-Arbez, Department of Genetic Medicine and Development, University Medical School Geneva, 1, rue Michel Servet, 1211 Geneva, Switzerland Tel: +41 22 379 5655; fax: +41 22 379 5706; e-mail: [email protected] Blood Coagulation & Fibrinolysis: March 2011 - Volume 22 - Issue 2 - p 148-150 doi: 10.1097/MBC.0b013e32834330d9 Buy Metrics Abstract Congenital afibrinogenemia is a rare autosomal recessive coagulation disorder characterized essentially by bleeding symptoms, but miscarriages and, paradoxically, thromboembolic events can also occur. Most reported mutations leading to congenital afibrinogenemia are located in FGA encoding the fibrinogen A α-chain. In this study, we analysed 12 individuals from a consanguineous Syrian family with reduced or absent fibrinogen levels: those with fibrinogen levels around 1 g/l (n = 7) were found to be heterozygous for a novel frameshift mutation in FGA exon 5 (c.1846 del A) and those with undetectable fibrinogen levels (n = 5) were homozygous for the same mutation. This novel frameshift mutation is the most C-terminal causative FGA mutation identified to date in afibrinogenemic patients. The resulting aberrant Aα-chain (p.Thr616HisfsX32) is most likely synthesized, but is less efficiently assembled and/or secreted into the circulation given the phenotype of asymptomatic hypofibrinogenemia in heterozygous individuals and bleeding diathesis in homozygous individuals. © 2011 Lippincott Williams & Wilkins, Inc.