title: Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis.
abstract: 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 woman, 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 activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Leu128 --> Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity.
authors.affiliation: Children's Hospital and the Central Laboratory, University of Würzburg, Würzburg, Germany. Schuster@mail.uni-wuerzburg.de
authors.forename: V
authors.initials: V
authors.lastname: Schuster
authors.forename: S
authors.initials: S
authors.lastname: Seidenspinner
authors.forename: P
authors.initials: P
authors.lastname: Zeitler
authors.forename: C
authors.initials: C
authors.lastname: Escher
authors.forename: U
authors.initials: U
authors.lastname: Pleyer
authors.forename: W
authors.initials: W
authors.lastname: Bernauer
authors.forename: E R
authors.initials: ER
authors.lastname: Stiehm
authors.forename: S
authors.initials: S
authors.lastname: Isenberg
authors.forename: S
authors.initials: S
authors.lastname: Seregard
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: A M
authors.initials: AM
authors.lastname: Mingers
authors.forename: C
authors.initials: C
authors.lastname: Schambeck
authors.forename: H W
authors.initials: HW
authors.lastname: Kreth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D001780:Blood Coagulation Tests; D002675:Child, Preschool; D003231:Conjunctivitis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010958:Plasminogen / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D010958:Plasminogen