title: Complex history of the discovery and characterization of congenital factor X deficiency.
abstract: Factor X (FX) plays a pivotal role in blood coagulation. FX represents the point where all coagulation systems converge and, once activated, it converts prothrombin into thrombin. The discovery and definition of FX are based on the description between 1956 and 1957 about three patients and their families with a peculiar defect later demonstrated to be almost identical. These patients were an American (Mr. Stuart), a British (Ms. Prower), and a Swiss with Italian background (infant Delia B). We stated "almost identical" because immunological and molecular biology studies subsequently revealed that even though the basic clotting defect was identical, the FX protein level and the mutation were different in each case. Mr. Stuart had no FX protein in his plasma and the mutation was Val298Met (homozygote). Ms. Prower instead had a normal level of FX protein and the mutation was Arg287Trp + Asp282Asn (compound heterozygote). Unfortunately, the status of the Swiss patient in this regard is not known. Subsequent studies described a few major variants (FX Friuli, FX Melbourne, FX Padua, and other similar patients), which showed peculiar activation patterns (FX Friuli had a normal Russell viper venom clotting time; FX Melbourne was defective only in the intrinsic coagulation system; FX Padua, on the contrary, was defective only in the extrinsic coagulation system). All these studies have informed on the great heterogeneity and complexity of the FX defect. The story of the discovery and classification of FX deficiency has contributed considerably to our understanding of blood coagulation. The three original families and the families of the major variants, together with the researchers that discovered them, should be remembered with deep respect and gratitude.
authors: Department of Medicine, University of Padua Medical School, Padua, Italy.
authors: Antonio
authors: A
authors: Girolami
authors: Department of Medicine, University of Padua Medical School, Padua, Italy.
authors: Elisabetta
authors: E
authors: Cosi
authors: Department of Medicine, University of Padua Medical School, Padua, Italy.
authors: Luisa
authors: L
authors: Sambado
authors: Division of Medicine, Padua City Hospital, Padua, Italy.
authors: Bruno
authors: B
authors: Girolami
authors: Department of Medicine, University of Padua Medical School, Padua, Italy.
authors: Maria Luigia
authors: ML
authors: Randi
mesh_terms: D019943:Amino Acid Substitution; D005170:Factor X / Q000235:genetics / Q000266:history / Q000378:metabolism; D005171:Factor X Deficiency / Q000145:classification / Q000235:genetics / Q000266:history / Q000378:metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D020125:Mutation, Missense
chemical_list: D005170:Factor X