Gelatinous drop-like corneal dystrophy in a child with developmental delay: clinicopathological features and exclusion of the M1S1 gene

Abstract

Aims Gelatinous drop-like corneal dystrophy (GDLD) is an early-onset, autosomal recessive condition characterised by amyloid deposits within the cornea. We report the histopathological and molecular genetic findings in a Caucasian child with GDLD who also exhibited global developmental delay. Methods Bilateral lamellar keratoplasty was carried out at age 6 and 7 years. Tissue was fixed for light and electron microscopy, including immunoelectronmicroscopy. The coding region of the M1S1 gene was screened for mutations in the affected proband and available relatives, using DNA extracted from mouthwashes. Results Nodular deposits, which were present subepithelially and in the central superficial stroma, stained typically for amyloid with PAS and Congo red. A nodular deposit of amyloid, together with large amounts of lactoferrin and sparse amounts of keratoepithelin (big-h3), was present in the central superficial stroma, causing destruction of Bowman's layer and elevation of the thinned, degenerate epithelium. Around the deposit zone, the stroma exhibited large numbers of thick filamentous proteoglycan deposits. While the affected child was homozygous for a novel A1133 C singlenucleotide polymorphism (SNP) that resulted in an aspartic acid to alanine substitution at position 173 of the M1S1 coding sequence, this polymorphism was also found at relatively high frequency in a sample of normal controls, enabling exclusion of the M1S1 gene as the disease locus. Conclusion Increased epithelial permeability in GDLD may be explained in part by an altered membrane permeability of the superficial epithelial cells. An association with developmental delay has not been reported previously.

Morphological and histopathological changes in gelatinous drop‐like corneal dystrophy during a 15‐year follow‐up

“…1E). Electron microscopy showed subepithelially abundant and irregularly arranged microfibrils of amyloid, similarly to observations by Akhtar et al (2005). Degenerated and partially vital macrophages seemed to contain dense substances such as those reported by Kanai & Kaufman (1982).…”

“…Analysis of the right cornea showed a partially thinned epithelium, destruction of Bowman's membrane and substantial amounts of subepithelial amyloid with nodular or string-like features (Fig. 1D), similar to features reported by Gartry et al (1989) and Akhtar et al (2005). The corneal stroma was compressed and oedematous.…”

“…1D), similar to features reported by Gartry et al (1989) and Akhtar et al (2005). The corneal stroma was compressed and oedematous.…”

Gelatinous Drop-Like Corneal Dystrophy – 2 Clinical Cases

“…B. Lactoferrin) aus dem Tränenfilm unter das Epithel gelangen, tropfenartig aggregieren und Epithel und Stroma schädigen. Ob die erhöhte Permeabilität primär transzellulär oder interzellulär bedingt ist, ist noch nicht abschließend geklärt [16].…”

“…Dies ist relevant, da der Abbruch der Translation hierbei deutlich später erfolgt als in der Q118X-Mutation und spricht dafür, dass die Transmembran-und PIP2-Domäne nahe des C-Terminus von TACSTD2 für dessen Funktion von Bedeutung ist. Zu erwähnen ist ein gut charakterisierter Fallbericht eines 6-jährigen kaukasischen Jungen mit GDLD und Entwicklungsverzögerung, bei dem eine kausale Beteiligung des TACSTD2-Gens ausgeschlossen wurde [16].…”