New molecular defects in the gamma subdomain of fibrinogen D-domain in four cases of (hypo)dysfibrinogenemia: fibrinogen variants Hannover VI, Homburg VII, Stuttgart and Suhl.
Four new molecular abnormalities in the gamma subdomain of the D domain elucidated in three unrelated thrombophilic patients and in one asymptomatic case of hypofibrinogenemia are reported: fibrinogen Suhl, gamma 326, Cys-->Tyr, fibrinogen Hannover VI, gamma 336 Met-->Ile, fibrinogen Stuttgart, gamma 345, Asn-->Asp and fibrinogen Homburg VII, gamma 354,Tyr-->Cys. In all cases, fibrin polymerization in plasma is impaired. In the case of fibrinogen Suhl, there was a normalization of fibrin polymerization in plasma at higher Ca(2+) concentration. The protective effect of Ca(2+) on plasmic degradation of fibrinogen was incomplete with all three variants. The fibrinogen molecules in variants Homburg VII and Suhl contain covalently bound albumin. Fibrin clot structure was abnormal in case of variant Homburg VII, with finer and more branched fibers forming a less porous clot. Experimental data indicate possible effects of the molecular abnormalities on Ca(2+)-binding, D-E interaction and lateral association of protofibrils.
Meyer
Michael
M
Dept. Biomedical Engineering, University of Applied Sciences (FH), Carl-Zeiss-Promenade 2, D-0745 Jena, Germany. michael.meyer@fh-jena.de
Franke
Kathrin
K
Richter
Walter
W
Steiniger
Frank
F
Seyfert
Ulrich T
UT
Schenk
Joachim
J
Treuner
Jörn
J
Haberbosch
Werner
W
Eisert
Roswit
R
Barthels
Monika
M
D000328:Adult; D000418:Albumins / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005337:Fibrin / Q000096:biosynthesis / Q000648:ultrastructure; D005340:Fibrinogen / Q000737:chemistry* / Q000235:genetics*; D005341:Fibrinolysin / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019851:Thrombophilia / Q000235:genetics*; D013997:Time Factors
D000418:Albumins; D008024:Ligands; D005337:Fibrin; D005340:Fibrinogen; D005341:Fibrinolysin; D002118:Calcium