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L.H. Suh, J. Paul, I.H. Maumenee, A.S. Jun, S. Chakravarti; Lumican Mutation Analysis of Patients with Cornea Plana . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1524.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To screen for lumican gene mutations in patients with cornea plana, a condition that resembles the lumican–null mouse phenotype. Lumican is a small leucine–rich repeat proteoglycan (SLRP) highly expressed in the corneal stroma and encoded on chromosome 12 (3 exons and 2 introns). Absence of lumican expression in mice has been shown to cause stromal thinning and disorganization of stromal collagen matrices with subsequent corneal opacification. Mutations in keratocan, another SLRP related to lumican, have been linked to cornea plana type 2. Phenotypic similarities in lumican–deficient mice with cornea plana make lumican a candidate gene for mutation analysis in patients with corneal stromal abnormalities. Methods: PCR analysis using upstream (A) and downstream (B) primers flanking exon 2 (most conserved exon encoding 86% of the protein sequence) was performed on DNA samples from 3 individuals with cornea plana and 7 unaffected relatives (total of 10 samples from 3 pedigrees in which keratocan mutations were excluded) obtained from the Johns Hopkins Center for Hereditary Eye Disease. Transmission patterns of the 3 pedigrees were autosomal dominant, presumed autosomal recessive, and autosomal recessive with consanguinity. PCR products amplified with primer A, an 18 bp intronic sequence 265 bps upstream of exon 2, and primer B, an 18 bp intronic sequence 250 bps downstream of exon 2, were analyzed via automated fluorescent DNA sequencing methods. Results: No mutations in exon 2 of the lumican gene were found in 10 DNA samples from 3 cornea plana pedigrees. Lumican sequencing will be performed on other patients and pedigrees with cornea plana and other corneal stromal abnormalities. Conclusions: Lumican is a strong candidate gene to screen for mutations in individuals with cornea plana demonstrated by the phenotypic similarities in lumican–null mice. Lumican sequence analysis of additional individuals and their relatives with cornea plana or other corneal stromal abnormalities may reveal pathogenic mutations in these disorders. Identification of such mutations may provide additional insights into the role of lumican in modulating normal collagen fibril architecture in the corneal stroma.
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