Molecular characterization of a factor VII deficient patient supports the importance of the second epidermal growth factor-like domain

Giovanna D'Andrea, Anna Bossone, Maria Rosaria Lupone, Flora Peyvandi, Giovanna Maisto, Fabio Perricone, Elvira Grandone, Maurizio Margaglione

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives. Although a large number of gene mutations have been characterized in patients with factor VII (FVII) deficiency, few naturally occurring mutations have been described in epidermal growth factor (EGF)-like domains. We investigated a 6-year old Italian girl who had low functional and antigenic FVII plasma levels. Design and Methods. Plasma levels of FVII activity and antigen were evaluated in the propositus and her relatives. Mutation screening was performed by sequencing the FVII gene. The effect of the identified FVII mutations was investigated by protein expression in transfected cells. Results The propositus was shown to be a compound heterozygote for a known (Arg110Cys) and a novel (Asp123Tyr) missense mutation both occurring in the second EGF-like domain. In transfected cells, expression of the Arg110Cys mutation reduced the amount of intracellular and secreted FVII protein (48% and 18%, respectively). Likewise, cells transfected with the Asp123Tyr mutation gave rise to low intracellular (40%) and extracellular(4%) FVII antigen levels. In conditioned media, FVII procoagulant activity was reduced accordingly (10% and

Original languageEnglish
Pages (from-to)979-984
Number of pages6
JournalHaematologica
Volume89
Issue number8
Publication statusPublished - Aug 2004

Keywords

  • Bleeding
  • EGF-like domain
  • Factor VII
  • Gene
  • Mutations

ASJC Scopus subject areas

  • Hematology

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