Ligneous conjunctivitis is an autosomal recessive inherited disease caused by mutations in the plasminogen (PLG) gene. Herein, we report a girl affected by this disorder, caused by a homozygous deletion of 14 base pairs in exon 5 of the PLG gene.
A 2-year-old Mexican girl, product of the fourth pregnancy of second-grade consanguineous parents with no relevant family history, was cared for at the Service of Ophthalmology of the University Hospital, Universidad Autónoma de Nuevo León, because of a refractory bilateral conjunctivitis noticed when she was 2 months of age. The physical examination revealed chronic inflammation of the eyelids and synechia of the tarsal and bulbar conjunctivae with hard pseudomembranes in both eyes; the rest of the examination results were normal. The parents did not show any abnormality in the eyes or facial mucous epithelia. The patient required surgical removal of the pseudomembranes after failing medical treatments with topical antibiotics and corticosteroids.
The evaluation of the fibrinolytic route demonstrated very low concentration of plasmatic plasminogen (<1 mg/dL [<0.113 μmol/L]; reference range, 7-17 mg/dL [0.791-1.921 μmol/L]) and plasminogen functional activity (6%; reference range, 75%-140%), confirming the diagnosis of ligneous conjunctivitis. The patient and her parents were studied for abnormalities in the PLG gene located at 6q26. Genomic DNA were isolated from peripheral blood and DNA samples were amplified by polymerase chain reaction using different sets of primer pairs designed in the Department of Biochemistry for analysis of exons 2, 5, 7, 10, 13, 14, 15, and 17 of the PLG gene. All amplicons included exon-intron boundaries. Polymerase chain reaction products were purified and sequenced in an automated DNA sequencer (Li-Cor DNA 4200; Li-Cor Inc, Lincoln, Neb) and confirmed by restriction fragment length polymorphism analysis. This study showed a homozygous nucleotide deletion of 14 base pairs in exon 5 of the PLG gene in the patient, which creates a stop codon at position 145 of the protein. The deletion eliminates a restriction site for PstI present in the wild-type allele. After digestion with PstI (New England Biolabs, Inc, Ipswich, Mass), amplicons were electrophoresed in 2.5% agarose gel and visualized by ethidium bromide staining. Both parents were heterozygous for the mutation (Figure).
Deletion of 14 base pairs (bp) in exon 5 of the plasminogen (PLG) gene. A, The sequence on the left (control sample) shows the segment that is deleted in the homozygous patient (5′-GAACTACTGCAGGA-3′) sequence on the right. Note that the wild-type segment harbors a restriction site for PstI. B, A restriction fragment length polymorphism analysis of exon 5 amplicons with PstI demonstrates the genotypes for the mutation in the family. The mutant (uncut) allele generates a 211-bp fragment, while the wild-type allele produces fragments of 143 and 82 bp. Lane M, 100-bp ladder; lane 1, patient + PstI; lane 2, healthy control + PstI; lane 3, healthy control undigested; lane 4, patient's mother + PstI; lane 5, patient's father + PstI.
Ligneous conjunctivitis is a rare disorder characterized by recurrent lesions of hard consistency in the mucous membranes, which have a negative effect on homeostatic fibrinolysis because of mutations in the PLG gene. This disorder is usually detected in young children with recurrent conjunctivitis due to pseudomembranes that evolve to hard nodular masses of woodlike consistency.1 Ligneous conjunctivitis has an autosomal recessive pattern of transmission and several mutations in the PLG locus have been demonstrated in patients with this disorder.1 A mutation screening performed on the patient and her parents demonstrated a nonreported, homozygous, 14–base pair deletion in exon 5 of the PLG gene, which generates an early stop in the 5′ region of the gene. One recent report suggests a possible “hot spot” region around the Cys133-Cys157 in the PLG gene.2 We hypothesize that this homozygous mutation results in the synthesis of a truncated plasminogen molecule in the liver that is quickly degraded,3 a finding that correlates with the early onset and the severity of the eye abnormalities. Despite this physiologic defect, it is noticeable that the patient does not show involvement in other organs besides the eyes.
Correspondence: Dr Ortiz-López, Department of Biochemistry, School of Medicine, Universidad Autónoma de Nuevo León, Ave Francisco I. Madero y Dr Aguirre Pequeño, Monterrey, Nuevo León, CP 64460, México (email@example.com).
Financial Disclosure: None reported.
Funding/Support: This work is supported by the Departments of Biochemistry and Ophthalmology, School of Medicine and University Hospital, Universidad Autónoma de Nuevo León.
Leyva-Castillo JM, Cavazos-Adame H, Rojas-Martínez A, López-Garza R, Espinoza MCF, Ortiz-López R. Ligneous Conjunctivitis in a Mexican Patient With a Mutation in the Plasminogen (PLG) Gene. Arch Ophthalmol. 2006;124(10):1500-1501. doi:10.1001/archopht.124.10.1500