Granular and lattice deposits in corneal dystrophy caused by R124C mutation of TGFBIp.
OBJECTIVE
Both granular and lattice deposits are present in Avellino corneal dystrophy (ACD), primarily associated with the R124H mutation of transforming growth factor-β-induced (TGFBIp). We investigated the presence of these deposits in other TGFBI mutations and the use of Thioflavin-T (ThT), a fluorescent amyloid stain for characterizing corneal amyloid deposits.


METHODS
Surgical corneal specimens of 3 unrelated patients clinically diagnosed with ACD were studied. Corneal sections from normal individuals and patients with prior lattice corneal dystrophy (LCD) were used as controls. Histochemical studies were performed with Congo red and Masson trichrome stains, and fluorescent imaging with scanning laser confocal microscopy was performed for ThT and anti-TGFBIp antibody staining.


RESULTS
Clinical and histopathological findings supported the diagnoses of ACD in these 3 cases in whom granular deposits stained with Masson trichrome and lattice deposits stained with ThT and Congo red showed birefringence and dichroism as expected. However, genotyping revealed a heterozygous R124C mutation in each case. In addition to classical stromal deposits, unique subepithelial TGFBIp aggregates, which stain with neither ThT nor trichrome, were observed. In control LCD sections, stromal deposits were stained with ThT but not with trichrome, confirming lack of granular deposits.


CONCLUSIONS
Our results demonstrate that both granular and lattice corneal deposits can be associated with R124C mutation in addition to the more common R124H mutation. An additional feature of nonhyaline, nonamyloid, TGFBIp subepithelial deposits might substantiate the categorization of such cases as a variant form of ACD. This study further validates ThT staining for detection of amyloid TGFBIp deposits.
Patel
Dhara A
DA
Departments of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Chang
Shu-Hong
SH
Harocopos
George J
GJ
Vora
Smita C
SC
Thang
Diep Huu
DH
Huang
Andrew J W
AJ
D000328:Adult; D000682:Amyloid / Q000378:metabolism; D000918:Antibody Specificity; D001120:Arginine; D052160:Benzothiazoles; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D003319:Corneal Stroma / Q000378:metabolism; D003545:Cysteine; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000276:immunology; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D019683:Penetrance; D013194:Staining and Labeling; D013844:Thiazoles; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000276:immunology; D000099222:betaIG-H3 Protein
D000682:Amyloid; D001120:Arginine; D052160:Benzothiazoles; D003545:Cysteine; D016326:Extracellular Matrix Proteins; D005456:Fluorescent Dyes; D013844:Thiazoles; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C009462:thioflavin T