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The prothrombin 20209 C→T mutation in Jewish‐Moroccan Caucasians: molecular analysis of gain‐of‐function of 3′ end processing
Author(s) -
DANCKWARDT S.,
HARTMANN K.,
KATZ B.,
HENTZE M. W.,
LEVY Y.,
EICHELE R.,
DEUTSCH V.,
KULOZIK A. E.,
BENTAL O.
Publication year - 2006
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2006.01885.x
Subject(s) - mutation , thrombophilia , allele , gene , medicine , pregnancy , genetics , thrombosis , endocrinology , microbiology and biotechnology , andrology , biology
Summary. Background: Mutations of the 3′ end mRNA‐processing 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 LightCycler TM 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.