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Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 773-775
BRIEF REPORT
Homozygous truncation of the fibrinogen A chain within the
coiled coil causes congenital afibrinogenemia
Andrew P. Fellowes,
Stephen O. Brennan,
Randi Holme,
Helge Stormorken,
Frank R. Brosstad, and
Peter M. George
From the Molecular Pathology Laboratory, Canterbury Health
Laboratories, Christchurch, New Zealand; and the Research Institute for
Internal Medicine, University of Oslo, Oslo, Norway.
The molecular basis of a novel congenital afibrinogenemia has been
determined. The proposita, the only affected member in a consanguineous
Norwegian family, suffers from a moderate to severe bleeding disorder
due to the total absence of any detectable fibrinogen. Dot blots of
solubilized platelets revealed a small amount of  chain but no A
or B chains, whereas no chains were detected in plasma dot blots.
DNA sequencing of the A chain gene revealed a homozygous
C T transversion 557 nucleotides from the transcription
initiation site. This nucleotide change predicts the nonsense mutation
A 149 Arg (CGA)stop (TGA). Early truncation of the A
chain appears to result in defective assembly or secretion of
fibrinogen, probably due to the removal of the C-terminal disulfide ring residues that are critically required for the formation of a
stable 3-chained half molecule.
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