Aims: Gelatinous drop-like corneal dystrophy (GDLD) is an early-onset, autos omal recessive condition characterised by amyloid deposits within the cornea. We report the histopathological and molecular genetic findings in a Caucasian chil d with GDLD who also exhibited global developmental delay. Methods: Bilateral la mellar keratoplasty was carried out at age 6 and 7 years. Tissue was fixed for l ight and electron microscopy, including immunoelectronmicroscopy. The coding reg ion of the M1S1 gene was screened for mutations in the affected proband and avai lable relatives, using DNA extracted from mouthwashes. Results: Nodular deposits , which were present subepithelially and in the central superficial stroma, stai ned typically for amyloid with PAS and Congo red. A nodular deposit of amyloid, together with large amounts of lactoferrin and sparse amounts of keratoepithelin (βig-h3), was present in the central superficial stroma, causing destruction of Bowman’s layer and elevation of the thinned, degenerate epithelium. Around t he deposit zone, the stroma exhibited large numbers of thick filamentous proteog lycan deposits. While the affected child was homozygous for a novel A1133 C sing lenucleotide polymorphism (SNP) that resulted in an aspartic acid to alanine sub stitution at position 173 of the M1S1 coding sequence, this polymorphism was als o found at relatively high frequency in a sample of normal controls, enabling ex clusion of the M1S1 gene as the disease locus. Conclusion: Increased epithelial permeability in GDLD may be explained in part by an altered membrane permeabilit y of the superficial epithelial cells. An association with developmental delay h as not been reported previously.
展开▼
