The prothrombin 20209 c fi t mutation in jewish-moroccan caucasians: Molecular analysis of gain-of-function of 3' end processing

S. Danckwardt, K. Hartmann, B. Katz, M. W. Hentze, Y. Levy, R. Eichele, V. Deutsch, A. E. Kulozik, O. Ben-Tal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Mutations of the 3' end mRNAprocessing signal of the prothrombin (F2) gene have been reported to cause elevated F2 plasma concentrations, thrombosis, and complications of pregnancy. Whereas the common F2 20210*A mutation is almost exclusively found in Caucasians, the F2 20209*T mutation has been reported in Afro-Americans and Afro-Caribbeans only. Patients and methods: Using LightCyclerTM technology, three unrelated Jewish-Moroccan patients tested for obstetric complications were found to be carriers of the F2 20209*T allele. A detailed molecular analysis was performed to identify the functional impact of this mutation. Results: We report three unrelated women of Jewish-Moroccan origin with a F2 20209*T mutation and fetal loss or infertility. The functional analysis revealed that the F2 20209*T mutation stimulates 3' end processing and up-regulates prothrombin protein expression as assessed by a highly sensitive luminescence-based reporter system. Conclusions: This is the first report of 20209*T in Caucasians, and functional analysis demonstrates that F2 20209*T falls into a general category of mutations of the F2 gene, which may possibly contribute to thrombophilia and complications of pregnancy by interfering with a tightly balanced architecture of non-canonical F2 3' end formation signals.

Original languageEnglish
Pages (from-to)1078-1085
Number of pages8
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume4
Issue number5
DOIs
StatePublished - 1 May 2006
Externally publishedYes

Keywords

  • Fetal loss
  • Infertility
  • Mrna processing
  • Polyadenylation
  • Prothrombin (F2) 20209
  • T
  • Thrombophilia

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