Abstract
We report a novel mutation in Factor X (FX) gene which results in a phenotype without
any bleeding tendency. The proband has been found to be a compound heterozygote between
a novel FX true deficiency (Gly380→Arg) and a previously reported dysfunctional mutation Ser334→Pro (FX Marsiglia). Prothrombin time (PT) and partial thromboplastin time (PTT) were
moderately prolonged and were fully corrected by the addition of normal serum. Her
FX activity level varied between 8% and 19% of normal according to the method used
whereas the FX antigen level was 40% of the normal control value. All the exons and
intron/exon junctions of the FX gene were studied using a combined approach of polymerase
chain reaction and conformation sensitive gel electrophoresis. A transversion G to
A in exon 8 resulting in the replacement of Gly380 by Arg was found in the proband,
in the father and in a proband's brother, whereas heterozygous FX Marsiglia was present
in the proband's mother and her sister. Gly380 is strictly linked to Ser379, a component
of the catalytic triad. The substitution of Gly for Arg causes the introduction of
a large charged amino acid which could affect the catalytic function of FX leading
to secretion problem, accounting for the cross-reactive material (CRM) negative phenotype.
Keywords
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Article info
Publication history
Accepted:
August 21,
2001
Received in revised form:
August 21,
2001
Received:
June 20,
2001
Identification
Copyright
© 2001 Elsevier Science Ltd. Published by Elsevier Inc. All rights reserved.
