title: Two novel fibrinogen variants in the C-terminus of the Bβ-chain: fibrinogen Rokycany and fibrinogen Znojmo.
abstract: Hereditary dysfibrinogenemia is a rare disorder wherein an inherited abnormality in fibrinogen structure may result in defective fibrin function and/or structure. Congenital hypofibrinogenemia is a rare autosomal bleeding disorder, either recessive or dominant, characterized by a low fibrinogen plasma level. A 28-year-old asymptomatic woman (fibrinogen Rokycany) and a 54-year-old man with thrombosis and pulmonary embolism (fibrinogen Znojmo) were investigated for a suspected fibrinogen mutation after abnormal coagulation tests results were obtained. DNA sequencing showed the heterozygous point mutation Bβ Asn351Lys in fibrinogen Rokycany and the heterozygous point mutation Bβ Arg237Ser in fibrinogen Znojmo, respectively. The kinetics of fibrinopeptide release was found to be normal in both cases. Fibrinolysis was impaired in the Znojmo variant. The average fibril diameters of Znojmo fibrin was slightly increased, but not differing significantly from normal; formed by less fibrils with abrupt fibril terminations. Rheological studies revealed a softer clot. Rokycany fibrin was formed by significantly narrower fibrils than normal fibrin; and the clot was denser than the control clot. Rheological studies revealed a stiffer clot. Impaired fibrinolysis and abnormal clot morphology may be the cause of thrombotic episodes in the patient with Znojmo mutation. New cases of hypofibrinogenemia and dysfibrinogenemia, found by routine coagulation testing, were genetically identified as a novel fibrinogen variants Bβ Asn351Lys (fibrinogen Rokycany) and Bβ Arg237Ser (fibrinogen Znojmo), respectively.
authors.affiliation: Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Praha 2, Czech Republic. kotlinr@uhkt.cz
authors.forename: Roman
authors.initials: R
authors.lastname: Kotlín
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Reicheltová
authors.forename: Jirí
authors.initials: J
authors.lastname: Suttnar
authors.forename: Peter
authors.initials: P
authors.lastname: Salaj
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hrachovinová
authors.forename: Tomás
authors.initials: T
authors.lastname: Riedel
authors.forename: Martin
authors.initials: M
authors.lastname: Malý
authors.forename: Milan
authors.initials: M
authors.lastname: Oravec
authors.forename: Jan
authors.initials: J
authors.lastname: Kvasnicka
authors.forename: Jan Evangelista
authors.initials: JE
authors.lastname: Dyr
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D015241:Fibrinogens, Abnormal / Q000235:genetics*; D018056:Hemorheology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D013927:Thrombosis / Q000209:etiology
chemical_list: C115499:BBeta fibrinogen; D015241:Fibrinogens, Abnormal; C555480:fibrinogen Rokycany; C555481:fibrinogen Znojmo; D005340:Fibrinogen