Fibrinogen Cordoba I: A gammaArg 275 His substitution associated with defective polymerization

GUGLIELMONE, HUGO; MINOLDO S; JARCHUM GD; ABATE DAGA, DANIEL; BOCCO JOSE LUIS

THROMBOSIS RESEARCH

Elsevier

Lugar: Orlando - USA; Año: 2007 vol. 121 p. 429 - 430

0049-3848

Human fibrinogen (Fg) is a 340 kDa glycoprotein and is composed of three pairs of similar but not identical disulfide-bound polypeptides known as Aƒ¿, BƒÀ, and ƒÁ chains [1,2]. TheƒÁ chain contains several sites that are crucial for normal fibrin polymerization, including the gah polymerization site which aligns the fibrin monomers into half-staggered protofibrils; the D:D interface which is necessary for proper end-to-end alignment of fibrin molecules in polymers assembling; a high-affinity calcium binding and, activated factor XIII cross-linking sites which catalyzes the formation of ƒÁ-dimers by introducing covalent bonds [3]. More than 40 different gene mutations leading to amino acid substitutions within the polypeptide ƒÁ chain were reported and the Arg 275 substitution being the second most common mutation found in this disease [4]. Here, we report a 45-year-old woman showing dysfibrinogenaemia found in a routine coagulation screening. The patient had a history of easy bruising as well as episodes of heavy menstrual bleeding. Her dysfibrinogenaemia was detected prior to the surgical extirpation of the thyroid gland and was confirmed 1 year later when she underwent hysterectomy. The mutation G¨A, leading to Arg¨His substitution, was found at the nucleotide 7476 of the gene encoding the ƒÁ-chain, while no changes were found in the regions analyzed for ƒ¿ and ƒÀ genes. These results demonstrate that the propositus, her father and brother carried a heterozygous point mutation causing an Arg 275¨His substitution in the polypeptide chain.