Clinical and molecular characterisation of 21 patients affected by quantitative fibrinogen deficiency

Rosanna Asselta, Manuela Platè, Michela Robusto, Munira Borhany, Ilaria Guella, Giulia Soldà, Abdolreza Afrasiabi, Marzia Menegatti, Tahir Shamsi, Flora Peyvandi, Stefano Duga

Research output: Contribution to journalArticle

Abstract

Fibrinogen is a plasma glycoprotein mainly synthesised by hepato-cytes and circulating as a 340-kDa hexamer consisting of two sets of three different polypeptide chains (Aa, Bp, and y, encoded by the FGA, FGB, and FGG gene, respectively). Congenital afibrinogenaemia and hypofibrinogenaemia are rare bleeding disorders characterised by abnormally low levels of functional and immunoreactive fibrinogen in plasma, associated with haemorrhagic manifestations of variable severity. While afibrinogenaemia is caused by mutations in the homozygous or compound heterozygous state in one of the three fibrinogen genes, hypofibrinogenaemia is generally due to heterozygous mutations, and is usually characterised by a milder phenotype. The mutational spectrum of these quantitative fibrinogen disorders includes large deletions, point mutations causing premature termination co-dons, and missense mutations often affecting fibrinogen assembly and/or secretion. Here we report the clinical and molecular characterisation of 13 unrelated afibrinogenaemic and eight hypofibrino -genaemic patients, leading to the identification of 17 different mutations (10 hitherto unknown). All the newly-identified missense and splicing mutations were in vitro expressed to verify their pathogenic role. Our data increase the number of mutations causing quantitative fibrinogen deficiencies by about 7%. The high number of private mutations identified in the analysed probands indicates that the full mu-tational screening of the three fibrinogen genes is still required for molecular diagnosis.

Original languageEnglish
Pages (from-to)567-576
Number of pages10
JournalThrombosis and Haemostasis
Volume113
Issue number3
DOIs
Publication statusPublished - 2015

Keywords

  • Afibrinogenaemia
  • Expression experiments
  • Hypofibrinogenaemia
  • Mutational screening

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

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