title: Whole-exome sequencing of a patient with severe and complex hemostatic abnormalities reveals a possible contributing frameshift mutation in C3AR1.
abstract: The increasing availability of genome-wide analysis has made it possible to rapidly sequence the exome of patients with undiagnosed or unresolved medical conditions. Here, we present the case of a 64-yr-old male patient with schistocytes in the peripheral blood smear and a complex and life-threatening coagulation disorder causing recurrent venous thromboembolic events, severe thrombocytopenia, and subdural hematomas. Whole-exome sequencing revealed a frameshift mutation (C3AR1 c.355-356dup, p.Asp119Alafs*19) resulting in a premature stop codon in C3AR1 (Complement Component 3a Receptor 1). Based on this finding, atypical hemolytic uremic syndrome was suspected because of a genetic predisposition, and a targeted treatment regime with eculizumab was initiated. Life-threatening hemostatic abnormalities would most likely have persisted had it not been for the implementation of whole-exome sequencing in this particular clinical setting.
authors.affiliation: Department of Hematology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark;
authors.forename: Eva
authors.initials: E
authors.lastname: Leinøe
authors.affiliation: Department of Hematology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark;
authors.forename: Ove Juul
authors.initials: OJ
authors.lastname: Nielsen
authors.affiliation: Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Jønson
authors.affiliation: Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Rossing
keywords: acute disseminated intravascular coagulation; recurrent deep vein thrombosis