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Blood, 15 July 2001, Vol. 98, No. 2, pp. 358-367
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Five novel mutations in the gene for human blood coagulation
factor V associated with type I factor V deficiency
Richard van Wijk,
Karel Nieuwenhuis,
Marijke van den
Berg,
Eric G. Huizinga,
Brenda B. van der Meijden,
Rob J. Kraaijenhagen, and
Wouter W. van Solinge
From the Department of Clinical Chemistry, University
Medical Center, Utrecht; Department of Hematology, University Medical
Center, Utrecht; Van Creveldkliniek, Utrecht Department of Crystal and
Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht
University, Utrecht, The Netherlands; Department of Clinical Chemistry,
Ziekenhuis Eemland, Amersfoort, The Netherlands.
Coagulation factor V (FV) plays an important role in maintaining
the hemostatic balance in both the formation of thrombin in the
procoagulant pathway as well as in the protein C anticoagulant pathway. FV deficiency is a rare bleeding disorder with variable phenotypic expression. Little is known about the molecular basis underlying this disease. This study identified 5 novel mutations associated with FV deficiency in 3 patients with severe FV deficiency but different clinical expression and 2 unaffected carriers. Four mutations led to a premature termination codon either by a nonsense mutation (single-letter amino acid codes): A1102T, K310Term. (FV Amersfoort) and C2491T, Q773Term. (FV Casablanca) or a
frameshift: an 8-base pair deletion between nucleotides 1130 and
1139 (FV Seoul1) and a 1-base pair deletion between
nucleotides 4291 and 4294 (FV Utrecht). One mutation was a novel
missense mutation: T1927C, C585R (FV Nijkerk), resulting in the absence
of mutant protein despite normal transcription to RNA. Most likely, an
arginine at this position disrupts the hydrophobic interior of the FV
A2 domain. The sixth detected mutation was a previously reported missense mutation: A5279G, Y1702C (FV Seoul2). In all
cases, the presence of the mutation was associated with type I FV
deficiency. Identifying the molecular basis of mutations underlying
this rare coagulation disorder will help to obtain more insight into
the mechanisms involved in the variable clinical phenotype of patients with FV deficiency.
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