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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1639-1645
Severe Factor VII Deficiency Due to a Mutation Disrupting an Sp1
Binding Site in the Factor VII Promoter
Josephine A. Carew,
Eleanor S. Pollak,
Katherine A. High, and
Kenneth A. Bauer
From the Hematology-Oncology Section, Department of Medicine,
Brockton-West Roxbury Department of Veterans Affairs Medical Center,
and Harvard Medical School, Boston, MA; and the Departments of
Pediatrics and Pathology and Laboratory Medicine, University of
Pennsylvania and The Children's Hospital of Philadelphia, PA.
We have identified a point mutation in the promoter of the factor
VII gene responsible for a severe bleeding disorder in a patient from a
large French-Canadian family with known consanguinity. The proband has
an extremely low plasma level of factor VII antigen and factor VII
coagulant activity (<1 percent of normal) and suffers from hemarthroses and chronic arthropathy. Sequencing of the patient's factor VII 5 flanking region, intron/exon junctions, and coding regions showed a homozygous point mutation, a C to G transversion at
position  94 relative to the translation start site. We show here
that this mutation prevented binding of transcription factor Sp1 and of
other nuclear proteins to this region of the factor VII promoter and
resulted in a 20-fold reduction in reporter gene expression in HepG2
cells. These data underscore the importance of this region of the
factor VII promoter for in vivo expression of the factor VII gene.
© 1998 by The American Society of Hematology.
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