Mutational screening of six afibrinogenemic patients: Identification and characterization of four novel molecular defects

Luca Monaldini, Rosanna Asselta, Stefano Duga, Flora Peyvandi, Mehran Karimi, Massimo Malcovati, Maria Luisa Tenchini

Research output: Contribution to journalArticle

Abstract

Congenital afibrinogenemia (CAF) is a rare coagulation disorder characterized by very low or unmeasurable levels of functional and immunoreactive fibrinogen in plasma, associated with a hemorrhagic phenotype of variable severity. It is transmitted as an autosomal recessive trait (prevalence 1: 1,000,000) and is invariantly associated with mutations affecting one of the three fibrinogen genes (FGA, FGB, and FGG, coding for Aα, Bβ, and γ chain, respectively). Fibrinogen is secreted by hepatocytes as a hexamer composed of two copies of each chain; the lack of one chain has been demonstrated to prevent its secretion. Most genetic defects causing afibrinogenemia are point mutations, whereas only three large deletions have been identified so far, all affecting the FGA gene. We here report the molecular characterization of six unrelated afibrinogenemic patients leading to the identification of eight different mutations, four hitherto unknown: a 4.1-Kb large deletion involving exon I of FGA (AC107385:g. 65682_69828del), two nonsense mutations (p.Trp229X in FGA and p.Trp266X in FGB), and an ins-del mutation (g. 1787_1789del3ins12) in FGA. The molecular characterization of CAF-causing genetic defects increases our understanding on the genetic basis of this disease and might be helpful for prenatal screening purposes, as also demonstrated during this study.

Original languageEnglish
Pages (from-to)546-551
Number of pages6
JournalThrombosis and Haemostasis
Volume97
Issue number4
DOIs
Publication statusPublished - Apr 2007

Keywords

  • Congenital afibrinogenemia
  • Fibrinogen
  • Large deletion
  • Mutational screening
  • Point mutations

ASJC Scopus subject areas

  • Hematology

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