A Correlation Between Thrombotic Disease and a Specific Fibrinogen Abnormality (Aα 554 Arg → Cys) in Two Unrelated Kindred, Dusart and Chapel Hill III

• Published in: Blood Vol. 84; no. 11; pp. 3709 - 3714
• Main Authors: Wada, Yasuo, Lord, Susan T.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.12.1994; The Americain Society of Hematology
• Subjects: Afibrinogenemia - blood; Afibrinogenemia - complications; Afibrinogenemia - genetics; Base Sequence; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Child; DNA Mutational Analysis; Fibrinogens, Abnormal - genetics; Fibrinogens, Abnormal - isolation & purification; Genetic Predisposition to Disease; Heterozygote; Humans; Male; Medical sciences; Miscellaneous; Molecular Sequence Data; Polymerase Chain Reaction; Pulmonary Embolism - etiology; Recurrence; Thromboembolism - etiology; Vascular disease; Case study; Human; DNA; Fibrinogen; Cardiovascular disease; Molecular biology; Thromboembolism; Coagulation factor
• DOI: 10.1182/blood.V84.11.3709.bloodjournal84113709
• ISSN: 0006-4971

For the first time, a correlation between a specific fibrinogen abnormality and the clinical symptoms of thrombosis has been found in unrelated families. These abnormal fibrinogens have been designated Dusart and Chapel Hill III. The abnormal fibrinogen Chapel Hill III was identified previously in a patient with thrombotic disease. We purified fibrinogen from small aliquots of patient and normal plasmas by a simple, rapid procedure. Coomassie stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated that fibrinogen Chapel Hill III contained several high molecular weight forms in addition to the two forms seen with normal fibrinogen. Immunoblot analysis of Chapel Hill III fibrinogen demonstrated that essentially all the high molecular weight forms react with antiserum to albumin. Immunoblot analysis of plasmin digests of Chapel Hill III fibrinogen demonstrated that albumin is linked to the C-terminus of the Aα chain. Using DNA analysis, we found that the patient is heterozygous for a single base change, resulting in the substitution Aα Arg 554 → Cys. This is the same change identified in fibrinogen Dusart. The Dusart family members who are heterozygous for this substitution also suffer from recurrent thrombotic disorders.