New molecular defects in the γ subdomain of fibrinogen D-domain in four cases of (hypo)dysfibrinogenemia: fibrinogen variants Hannover VI, Homburg VII, Stuttgart and Suhl
New molecular defects in the γ subdomain of fibrinogen D-domain in four cases of (hypo)dysfibrinogenemia: fibrinogen variants Hannover VI, Homburg VII, Stuttgart and Suhl
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四种（低）异常纤维蛋白原血症病例中纤维蛋白原 D 结构域 γ 亚结构域的新分子缺陷：纤维蛋白原变体汉诺威 VI、洪堡 VII、斯图加特和苏尔
DOI：
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发表时间：
2003
影响因子：
6.7
通讯作者：
M. Barthels
中科院分区：
文献类型：
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作者：
M. Meyer;Kathrin Franke;W. Richter;F. Steiniger;U. Seyfert;J. Schenk;J. Treuner;W. Haberbosch;R. Eisert;M. Barthels
总结报告了3例无关的血栓形成患者和1例无症状低纤维蛋白原血症患者D结构域γ亚结构域的4种新分子异常：纤维蛋白原苏尔，γ 326，Cys →Tyr，纤维蛋白原汉诺威VI，γ 336 Met →Ile，纤维蛋白原斯图加特，γ 345，Asn→Asp和纤维蛋白原洪堡VII，γ354，Tyr→Cys。在所有情况下，血浆中的纤维蛋白聚合受损。在纤维蛋白原苏尔的情况下，在较高的Ca 2+浓度下，血浆中的纤维蛋白聚合正常化。Ca 2+对纤维蛋白原的血浆降解的保护作用是不完全的所有三种变体。变体洪堡VII和苏尔中的纤维蛋白原分子含有共价结合的白蛋白。在变体洪堡VII的情况下，纤维凝块结构异常，具有更细和更多分支的纤维，形成较少孔隙的凝块。实验数据表明，可能的影响的分子异常的钙离子结合，D-E相互作用和侧协会的原纤维。
Summary Four new molecular abnormalities in the γ subdomain of the D domain elucidated in three unrelated thrombophilic patients and in one asymptomatic case of hypofibrinogenemia are reported: fibrinogen Suhl, γ 326,Cys →Tyr, fibrinogen Hannover VI, γ 336 Met →Ile, fibrinogen Stuttgart, γ 345, Asn→Asp and fibrinogen Homburg VII, γ354,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 Ca2+ concentration. The protective effect of Ca2+ 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 Ca2+-binding, D-E interaction and lateral association of protofibrils.