Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis

Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly wo man, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual a ctivity of 17%, 18%, and 17%, respectively. These subjects were compound-he terozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Le u(128) --> Pro, respectively. The other 2 patients, a 14-year-old boy and h is 19-year-old sister, who both presented with a severe course of the disea se, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were com pound-heterozygotes for a deletion mutation (del Lys(212)) and a splice sit e mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findi ngs show that certain compound-heterozygous mutations in the plasminogen ge ne may be associated with ligneous conjunctivitis. Our findings also sugges t that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functiona l residual activity. (C) 1999 by The American Society of Hematology.