Fibrinogen Osaka IV: a congenital dysfibrinogenemia found in a patient originally reported in relation to surgery, now defined to have an A alpha arginine-16 to histidine substitution.
We discovered a congenital heterozygous dysfibrinogen in a patient and reported this case in relation to surgery some time ago (Jpn J Surg (1988) 18:43-46). Further studies on the isolated abnormal population of fibrinogen derived from this patient have revealed that fibrinopeptide A was not cleaved by ancrod, a snake venom-derived thrombin-like enzyme, but by thrombin, slowly but completely. The released fibrinopeptide A components, being the A, AY, and AP peptides, were all found to be abnormal, as evidenced by slightly earlier elution positions on high-performance liquid chromatography, compared with the normal counterparts. By analyzing their amino acid sequence, we have identified an arginine to histidine substitution at position 16 of the A alpha chain, the thrombin cleavage site. Utilizing insolubilized abnormal fibrinogen, we confirmed that the polymerization site assigned to the central E domain, the "A" site, was exposed by thrombin, but not by ancrod. This dysfibrinogen, designated as fibrinogen Osaka IV, is the second abnormal molecule with an A alpha arginine-16 to histidine substitution identified among Japanese families.
Yamazumi
K
K
Division of Hemostasis and Thrombosis Research, Jichi Medical School, Tochigi, Japan.
Terukina
S
S
Matsuda
M
M
Kanbayashi
J
J
Sakon
M
M
Tsujinaka
T
T
D000347:Afibrinogenemia / Q000151:congenital / Q000235:genetics*; D000595:Amino Acid Sequence; D000721:Ancrod; D001120:Arginine / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D015241:Fibrinogens, Abnormal / Q000737:chemistry*; D005344:Fibrinopeptide A / Q000737:chemistry; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
D015241:Fibrinogens, Abnormal; C080534:fibrinogen Osaka IV; D005344:Fibrinopeptide A; D006639:Histidine; D001120:Arginine; D000721:Ancrod