title: The Unravelling of the Genetic Architecture of Plasminogen Deficiency and its Relation to Thrombotic Disease.
abstract: Although plasminogen is a key protein in fibrinolysis and several mutations in the plasminogen gene (PLG) have been identified that result in plasminogen deficiency, there are conflicting reports to associate it with the risk of thrombosis. Our aim was to unravel the genetic architecture of PLG in families with plasminogen deficiency and its relationship with spontaneous thrombotic events in these families. A total of 13 individuals from 4 families were recruited. Their genetic risk profile of thromboembolism was characterized using the Thrombo inCode kit. Only one family presented genetic risk of thromboembolism (homozygous carrier of F12 rs1801020 and F13A1 rs5985). The whole PLG was tested using Next Generation Sequencing (NGS) and 5 putative pathogenic mutations were found (after in silico predictions) and associated with plasminogen deficiency. Although we can not find genetic risk factors of thrombosis in 3 of 4 families, even the mutations associated with plasminogen deficiency do not cosegregated with thrombosis, we can not exclude plasminogen deficiency as a susceptibility risk factor for thrombosis, since thrombosis is a multifactorial and complex disease where unknown genetic risk factors, in addition to plasminogen deficiency, within these families may explain the thrombotic tendency.
authors.affiliation: Unit of Genomics of Complex Diseases, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Martin-Fernandez
authors.affiliation: Department of Haematology, Hospital General Universitario, Alicante, Spain.
authors.forename: Pascual
authors.initials: P
authors.lastname: Marco
authors.affiliation: Congenital Coagulopathies, Blood and Tissue Bank, Barcelona, Spain.|Molecular Diagnosis and Therapy, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Corrales
authors.affiliation: Unit of Genomics of Complex Diseases, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Pérez
authors.affiliation: Congenital Coagulopathies, Blood and Tissue Bank, Barcelona, Spain.|Molecular Diagnosis and Therapy, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Ramírez
authors.affiliation: Unit of Genomics of Complex Diseases, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: López
authors.affiliation: Congenital Coagulopathies, Blood and Tissue Bank, Barcelona, Spain.|Molecular Diagnosis and Therapy, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vidal
authors.affiliation: Unit of Genomics of Complex Diseases, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Soria
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010958:Plasminogen / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D013923:Thromboembolism / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
chemical_list: D010958:Plasminogen