title: Homozygous variant of antithrombin III: AT III Fontainebleau.
abstract: A qualitative defect of antithrombin III (AT III) was demonstrated in four members of a large Tunisian family by the discrepancy between a normal amount of antigen and decreased or absent heparin cofactor activity. The propositus, a 3-year-old girl, died from massive intracardiac thrombosis despite oral anticoagulant therapy. Heparin cofactor activity measured in the presence of thrombin or F. Xa was undetectable in her plasma. Anti-F. Xa activity was also absent when using low molecular weight heparin or a synthetic pentasaccharide, representing the binding site to AT III. The lack of affinity of the propositus AT III for heparin was demonstrated by two-dimensional immunoelectrophoresis and chromatography on heparin-Sepharose. The parents, first cousins, and the sister of the propositus also demonstrated a qualitative abnormality of AT III, with levels of heparin cofactor activity close to 50% of the normal range. Our data support the view that the abnormal protein was present at the heterozygous state in the parents and sister and at the homozygous state in the propositus. None of the affected family members had thrombotic episodes, except for the propositus. The name of AT III Fontainebleau is proposed for this variant.
mesh_terms: D000990:Antithrombin III / Q000235:genetics* / Q000302:isolation & purification; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D005170:Factor X / Q000378:metabolism; D015951:Factor Xa; D005260:Female; D014644:Genetic Variation; D006487:Hemostasis; D006493:Heparin / Q000494:pharmacology; D006720:Homozygote; D006801:Humans; D007122:Immunoelectrophoresis; D008297:Male; D010375:Pedigree
chemical_list: C050532:antithrombin III Fontainebleau; D000990:Antithrombin III; D005170:Factor X; D006493:Heparin; D015951:Factor Xa