In:
Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 92, No. 12 ( 2004), p. 1291-1295
Abstract:
The molecular basis of hypofibrinogenaemia was investigated in a 34-year-old woman and her 10-year-old daughter. DNA sequencing revealed a single heterozygous GCC→GTC transition in exon 8 of the fibrinogen γ gene in both subjects, predicting a novel γ289 Ala→Val substitution. Examination of fibrinogen γ chains by electrospray ionization mass spectrometry failed to detect the variant chain in plasma fibrinogen. Further evidence for its non-expression came from tryptic peptide mapping. The mutation predicts a mass increase of 28 Da in peptide T32, but only the normal (M+2H) ion was detected at 1418 m/z in the proposita. Our finding that γ289 is an important determinant of plasma fibrinogen levels highlights the role of mutational analysis in defining structurally important regions of the fibrinogen molecule. This case suggests that the highly conserved Ala289 is important in maintaining structure of the “a” polymerization site via hydrogen bonding to Thr371.
Type of Medium:
Online Resource
ISSN:
0340-6245
,
2567-689X
DOI:
10.1160/TH04-07-0409
Language:
English
Publisher:
Georg Thieme Verlag KG
Publication Date:
2004