Fibrinogen Kanazawa: a congenital dysfibrinogenaemia with delayed polymerization having a replacement of proline-18 by leucine in the A alpha-chain.
Congenital dysfibrinogenaemia was found in a 39-year-old female and her two children. The proposita, apparently heterozygous for this abnormality, had no episode of bleeding or thrombosis. The abnormal fibrinogen showed normal release of fibrinopeptides A and B but impaired polymerization of the fibrin monomer. Amino acid sequence analysis of the whole A alpha-chain isolated from fibrinogen Kanazawa showed a substitution of Leu for Pro at position 18 in the A alpha-chain. This substitution was corroborated by the analysis of the amino acid sequence which demonstrated the lysyl endopeptidase peptides derived from the A alpha-chain of fibrinogen Kanazawa. The minimal genetic exchange responsible for this substitution was a C----T transition in the middle position of the Pro codon. We conclude that Pro-18 in the A alpha-chain is crucial for the polymerization of the fibrin monomer.
Uotani
C
C
Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan.
Miyata
T
T
Kumabashiri
I
I
Asakura
H
H
Saito
M
M
Matsuda
T
T
Kajiyama
S
S
Iwanaga
S
S
D000328:Adult; D000595:Amino Acid Sequence; D001778:Blood Coagulation Disorders / Q000097:blood / Q000151:congenital*; D001780:Blood Coagulation Tests; D005260:Female; D015241:Fibrinogens, Abnormal / Q000737:chemistry / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism; D005345:Fibrinopeptide B / Q000378:metabolism; D006801:Humans; D007930:Leucine; D008969:Molecular Sequence Data; D011108:Polymers / Q000378:metabolism; D011392:Proline
D015241:Fibrinogens, Abnormal; D011108:Polymers; C071487:fibrinogen Kanazawa; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D011392:Proline; D007930:Leucine