An apparently higher molecular weight gamma-chain variant in a new
congenital abnormal fibrinogen Tochigi characterized by the replacement of
gamma arginine-275 by cysteine
N Yoshida, K Ota, M Moroi and M Matsuda
Institute of Hematology, Jichi Medical School, Tochigi, Japan.
A gamma-chain variant with an apparently higher molecular weight than the
normal gamma-chain was detected in a new congenital abnormal fibrinogen
with impaired polymerization of the fibrin monomer and with normal release
of fibrinopeptides A and B in a 51-year-old male. Purified fibrinogen
analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis
(SDS-PAGE) under the reduced condition in the system of Laemmli contained
two protein bands in the gamma-chain region (molecular weight, 50,500 as
compared with 50,000 for the normal), both with normal crosslinking
ability. The presence of two types of gamma- chains was more clearly
detected when reduced and carboxymethylated fibrinogen was analyzed by
SDS-PAGE or when reduced fragment D2 was analyzed on SDS-PAGE followed by
Western blotting, and identified by positive staining for anti gamma-chain
monoclonal antibody. Cyanogen bromide- or lysylendopeptidase-cleavage of
purified gamma-chains analyzed on reverse-phase high performance liquid
chromatography showed the decrease of one peptide compared with the normal
and the appearance of an abnormal peptide peak. Amino acid sequence
analysis demonstrated that the gamma arginine-275 of gamma-chain variant
was replaced by a cysteine. These data suggest that some regions or
conformations containing gamma 275 will affect the polymerization of fibrin
monomers. The propositus' two daughters had the same abnormal fibrinogen.
This unique inherited abnormal fibrinogen was designated as fibrinogen
Tochigi, and the gamma-chain variant as gamma Tochigi.
Volume 71,
Issue 2,
pp. 480-487,
02/01/1988
Copyright © 1988 by The American Society of Hematology
