Shigekiyo et al. (1993) identified a family with congenital HRG deficiency. The proband, a 43-year-old woman, suffered from right transverse sinus thrombosis during oral contraceptive treatment. Affected members of the family (5 in 3 generations) had plasma HRG ... Shigekiyo et al. (1993) identified a family with congenital HRG deficiency. The proband, a 43-year-old woman, suffered from right transverse sinus thrombosis during oral contraceptive treatment. Affected members of the family (5 in 3 generations) had plasma HRG levels 25 to 35% of normal. Shigekiyo et al. (1995) could demonstrate no abnormalities in hemostatic screening tests, activities of natural anticoagulants and fibrinolytic proteins, markers of thrombin and plasmin generation, plasma levels of platelet-specific proteins, thrombin times with various concentrations of bovine thrombin, prolongation of thrombin time after addition of heparin or dermatan sulfate, and contact activation of blood coagulation in 5 'affected' members of the family. Souto et al. (1996) described a family with decreased levels of HRG in 4 individuals of 3 generations. The family was brought to their attention by a woman who had developed pulmonary embolism twice at the age of 36 years. Her father had thrombosis of the central retinal artery at the age of 59 years. None of the individuals in the family was under drug therapy or affected by inflammatory diseases able to modify the plasma concentration of HRG. - Thrombophilia due to Elevated HRG Engesser et al. (1987) described a family with thrombophilia and elevated levels of HRG in 5 persons in 3 sibships of 2 generations. By history a third generation was affected, and the apparent involvement of a deceased member represented male-to-male transmission. Falkon et al. (1992) described a similar family in which high levels of the HRG protein was demonstrated. The family was brought to attention by a 41-year-old woman who had had recurrent thromboembolic disease starting at the age of 22 years. She was also shown to have elevation of plasminogen activator inhibitor-1 (PAI1; 173360), which was not detected in any other member of the family. Falkon et al. (1992) suggested that elevated HRG may not be a strong risk factor for venous thrombosis when it is not combined with another defect. Angles-Cano et al. (1993) found high levels of HRG and PAI1 in 8 and 10 members, respectively, of a family from which 4 of 7 members with both abnormalities had venous thromboembolism. On the basis of their studies, they concluded that the excess HRG was probably not related to the thromboembolic events. Hoffmann et al. (1993) found persistently elevated levels of plasma HRG in a 64-year-old female with a history of recurrent arterial thromboembolic events. Increased HRG was found in 8 of 17 relatives studied, but none of them had experienced thromboembolism. Increased HRG was inherited as an autosomal dominant. The plasma HRG of the proposita and 9 of her family members displayed abnormal binding to heparin, as assessed in a crossed affinity immunoelectrophoresis system; the usual increase in mobility after binding to heparin was absent. The binding of the variant HRG to plasminogen was normal. This was the first example of an abnormal HRG variant. The authors proposed the designation HRG-Eindhoven for the variant. Castaman et al. (1993) described 2 families with a history of thrombosis and high levels of HRG. The propositus of family 1 died of massive pulmonary embolism at age 34. His mother and maternal grandmother suffered from deep and superficial vein thrombosis (DVT/SVT) in their youth. High levels of HRG were found in the mother, 3 of the proband's sibs, and 2 of his nephews. In family 2, the proposita suffered from spontaneous DVT at age 24. The paternal grandmother and a paternal aunt had several episodes of SVT and DVT. High levels of HRG cosegregated with thrombotic symptoms. Ehrenforth et al. (1994) evaluated the prevalence of elevated plasma HRG levels over a 5-year period in 695 patients suffering from thrombophilia. The plasma level of HRG was consistently higher in 10.8% of all investigated patients than in a group of 60 healthy individuals. Familial elevation of HRG was found in 3 of 10 investigated families.
In a 43-year-old woman with HRG deficiency who suffered from right transverse sinus thrombosis during oral contraceptive treatment, Shigekiyo et al. (1998) identified a 429G-A transition, which caused a gly85-to-glu substitution (142640.0001) in the first cystatin-like domain of ... In a 43-year-old woman with HRG deficiency who suffered from right transverse sinus thrombosis during oral contraceptive treatment, Shigekiyo et al. (1998) identified a 429G-A transition, which caused a gly85-to-glu substitution (142640.0001) in the first cystatin-like domain of the protein. The mutation was found in members of her family with HRG deficiency but not in 50 unrelated healthy Japanese individuals.