Novel CHST6 gene mutations in 2 unrelated cases of macular corneal dystrophy.
OBJECTIVE
To investigate the possible mutations in the carbohydrate sulfotransferase 6 (CHST6) gene of 2 unrelated cases of macular corneal dystrophy (MCD) and to report atypical stromal deposits in one of them.


METHODS
Corneal tissues were stained with antisulfated keratan sulfate (KS), antitransforming growth factor beta 1-induced protein (TGFBIp), thioflavin-T, alcian blue, and Masson trichrome. Sequencing was performed to identify potential mutations in the CHST6 gene and the fourth and twelfth exons of the TGFBI gene.


RESULTS
Alcian blue staining revealed the presence of multiple subepithelial and intrastromal mucopolysaccharide deposits, confirming the diagnosis of MCD in both cases. Immunofluorescence staining in case 1 revealed the presence of sulfated KS only in the keratocytes and select endothelial cells, consistent with MCD type IA. Preferential expression of sulfated KS was observed in keratocytes and extracellular stromal matrix in case 2, consistent with MCD type II. Atypical subepithelial and superficial stromal deposits were observed in case 1, which stained positively with alcian blue, eosin, Masson trichrome, and thioflavin-T indicating the presence of hyaline and amyloid materials. CHST6 gene sequencing revealed 2 heterozygous mutations in case 1 (a p.Arg211Gln and a novel mutation of p.Arg177Gly) and a novel homozygous mutation of p.Pro186Arg in case 2. No mutations were found in exons 4 or 12 of the TGFBI gene in case 1.


CONCLUSIONS
Secondary hyalinosis and amyloidosis occur in a case of MCD type IA with a novel p.Arg177Gly mutation in CHST6. A novel p.Pro186Arg mutation in CHST6 is associated with MCD type II in an African American.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA.
Dhara A
DA
Patel
George J
GJ
Harocopos
Shu-Hong
SH
Chang
Smita C
SC
Vora
Anthony J
AJ
Lubniewski
Andrew Jw
AJ
Huang
D000328:Adult; D000423:Alcian Blue; D058227:Amyloidogenic Proteins / Q000378:metabolism; D000686:Amyloidosis / Q000473:pathology; D004396:Coloring Agents; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D015948:Keratoplasty, Penetrating; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013194:Staining and Labeling / Q000379:methods; D015238:Sulfotransferases / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics; D000097811:Carbohydrate Sulfotransferases; D000099222:betaIG-H3 Protein
D000423:Alcian Blue; D058227:Amyloidogenic Proteins; D004396:Coloring Agents; D016326:Extracellular Matrix Proteins; D015238:Sulfotransferases; D016212:Transforming Growth Factor beta; D000097811:Carbohydrate Sulfotransferases; D000099222:betaIG-H3 Protein
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