PLG – Ligneous Conjunctivitis

Ligneous conjunctivitis is a rare autosomal recessive mucosal disease characterized by fibrin-rich pseudomembranes on the tarsal conjunctiva and other mucous membranes. Plasminogen, encoded by PLG (HGNC:9071), is critical for fibrinolysis. Type I plasminogen deficiency due to biallelic PLG variants underlies the development of ligneous conjunctivitis, often presenting in infancy with occlusive hydrocephalus and oral or respiratory pseudomembranes (PMID:9242524).

1. Clinical Validity

Based on multiple unrelated families and over 17 probands with concordant phenotype–genotype correlations, the association between PLG pathogenic variants and ligneous conjunctivitis is Definitive. Homozygous and compound heterozygous LoF or missense PLG variants have been reported in Turkish, Chilean, Japanese, and Chinese patients, with segregation of recessive alleles in family members and consistent biochemical deficiency (PMID:10233898).

2. Genetic Evidence

Inheritance is autosomal recessive. Segregation analysis identified at least 2 additional affected siblings with compound-heterozygous variants in one family (PMID:10233898). Across studies, at least 10 unique PLG variants have been reported in homozygous or compound heterozygous states among 17 probands, including missense (e.g., c.704G>A (p.Arg235His)) and nonsense or frameshift alleles, demonstrating a broad variant spectrum without evidence for a single founder (PMID:9242524).

3. Functional Evidence

Plasminogen activity assays in patient plasma uniformly show severe reduction (<5–20% of normal), correlating with antigen deficiency. Functional fibrinolysis assays demonstrate impaired t-PA–mediated fibrin clot lysis in patients versus relatives and controls (PMID:32369847). In vitro expression of mutant plasminogen constructs reveals defective secretion and intracellular accumulation, establishing haploinsufficiency as the pathogenic mechanism (PMID:8978291).

4. Conflicting Evidence

No studies have refuted the PLG–ligneous conjunctivitis link. Variability in clinical severity appears related to residual plasminogen activity rather than alternative causes.

5. Integration and Clinical Utility

Biallelic PLG pathogenic variants cause a consistent phenotype of ligneous conjunctivitis with early onset and possible multi-organ pseudomembranes. Genetic testing for PLG should be considered in infants with recurrent pseudomembranous conjunctivitis and plasminogen deficiency. Functional assays guide prognosis and support therapeutic approaches, such as fresh frozen plasma or plasminogen replacement. Key take-home: Identification of homozygous or compound heterozygous PLG variants enables definitive diagnosis and informs multidisciplinary management to prevent mucosal complications and hydrocephalus.

References

• Blood • 1997 • Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous conjunctivitis. PMID:9242524
• Blood • 1999 • Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis. PMID:10233898
• Thrombosis and haemostasis • 2020 • Functional Fibrinolysis Assays Reveal Different Mechanisms underlying Plasminogen Dysfunction in Ligneous Conjunctivitis. PMID:32369847
• Ophthalmic genetics • 2021 • Novel homozygous mutation of plasminogen in ligneous conjunctivitis: a case report and literature review. PMID:33427557

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