Korean J Ophthalmol.  2013 Dec;27(6):454-458. 10.3341/kjo.2013.27.6.454.

A Case of Korean Patient with Macular Corneal Dystrophy Associated with Novel Mutation in the CHST6 Gene

• Lee YK
• Chang DJ
• Chung SK

• KMID: 1792082
• DOI: http://doi.org/10.3341/kjo.2013.27.6.454

Abstract

To report a novel mutation within the CHST6 gene, as well as describe light and electron microscopic features of a case of macular corneal dystrophy. A 59-year old woman with macular corneal dystrophy in both eyes who had decreased visual acuity underwent penetrating keratoplasty. Further studies including light and electron microscopy, as well as DNA analysis were performed. Light microscopy of the cornea revealed glycosaminoglycan deposits in the keratocytes and endothelial cells, as well as extracellularly within the stroma. All samples stained positively with alcian blue, colloidal iron, and periodic acid-Schiff. Electron microscopy showed keratocytes distended by membrane-bound intracytoplasmic vacuoles containing electron-dense fibrillogranular material. These vacuoles were present in the endothelial cells and between stromal lamellae. Some of the vacuoles contained dense osmophilic whorls. A novel homozygous mutation (c.613 C>T [p.Arg205Trp]) was identified within the whole coding region of CHST6. A novel CHST6 mutation was detected in a Korean macular corneal dystrophy patient.

Keyword

Carbohydrate sulfotransferase; Corneal dystrophies, hereditary; Microscopy, electron; Microscopy, polarized; Mutation, missense

MeSH Terms

Corneal Dystrophies, Hereditary/diagnosis/*genetics/metabolism
Corneal Keratocytes/ultrastructure
DNA/*genetics
DNA Mutational Analysis
Female
Humans
Microscopy, Electron
Middle Aged
*Mutation, Missense
Pedigree
Polymerase Chain Reaction
Republic of Korea
Sulfotransferases/*genetics/metabolism
DNA
Sulfotransferases

Figure

• 

  Fig. 1 Slit lamp photography of the patient (A,B). (A) Right eye and (B) left eye. Diffusely hazy corneas with bilateral opacities were observed. There were multiple irregular, grayish-white, dense, poorly delineated spots in the stroma. Slit lamp photography of the patient's son (C,D). (C) Right eye and (D) left eye. Haziness of the stroma with diffuse opacities was observed in both eyes. These findings were similar, but less severe in appearance compared to his mother's examination.

• 

  Fig. 2 Comparison between light microscopic appearances (×100). The arrows indicate positive findings for glycosaminoglycan. (A) Hematoxylin and eosin stain, (B) alcian blue stain, (C) colloidal iron stain, (D) periodic acid-Schiff stain, and (E) Masson's trichrome stain.

• 

  Fig. 3 Transmission electron microscopic findings. (A) Keratocyte distended by membrane-bound intracytoplasmic vacuoles containing electron dense fibrillogranular material (black arrow). Vacuole containing dense fibrillogranular material in the interstromal lamellae (white arrow). Asterisk indicates relatively normal keratocyte (scale bar, 2 µm). (B) Keratocyte with vacuoles containing dense osmophilic whorls (scale bar, 0.5 µm).

• 

  Fig. 4 Direct sequencing analysis of the coding region of CHST6. (A) DNA sequence of the patient. (B) DNA sequence of the patient's son. Sequence of the entire coding region of CHST6 revealed a change in the nucleotide at codon 205 (CGG→TGG). The same mutation was identified in the patient's son (p.Arg205Trp [c.613C>T]).

Reference

1. McTigue JW. The human cornea: a light and electron microscopic study of the normal cornea and its alterations in various dystrophies. Trans Am Ophthalmol Soc. 1967; 65:591–660.

2. Donnenfeld ED, Cohen EJ, Ingraham HJ, et al. Corneal thinning in macular corneal dystrophy. Am J Ophthalmol. 1986; 101:112–113.

3. Jee DH, Lee YD, Kim MS. Epidemiology of corneal dystrophy in Korea. J Korean Ophthalmol Soc. 2003; 44:581–587.

4. Santo RM, Yamaguchi T, Kanai A, et al. Clinical and histopathologic features of corneal dystrophies in Japan. Ophthalmology. 1995; 102:557–567.

5. Akama TO, Nishida K, Nakayama J, et al. Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene. Nat Genet. 2000; 26:237–241.

6. Dang X, Zhu Q, Wang L, et al. Macular corneal dystrophy in a Chinese family related with novel mutations of CHST6. Mol Vis. 2009; 15:700–705.

7. Weiss JS, Moller HU, Lisch W, et al. The IC3D classification of the corneal dystrophies. Cornea. 2008; 27:Suppl 2. S1–S83.

8. Snip RC, Kenyon KR, Green WR. Macular corneal dystrophy: ultrastructural pathology of corneal endothelium and Descemet's membrane. Invest Ophthalmol. 1973; 12:88–97.

9. Klintworth GK, Vogel FS. Macular corneal dystrophy: an inherited acid mucopolysaccharide storage disease of the corneal fibroblast. Am J Pathol. 1964; 45:565–586.

10. Hassell JR, Newsome DA, Krachmer JH, Rodrigues MM. Macular corneal dystrophy: failure to synthesize a mature keratan sulfate proteoglycan. Proc Natl Acad Sci U S A. 1980; 77:3705–3709.

11. El-Ashry MF, Abd El-Aziz MM, Wilkins S, et al. Identification of novel mutations in the carbohydrate sulfotransferase gene (CHST6) causing macular corneal dystrophy. Invest Ophthalmol Vis Sci. 2002; 43:377–382.

12. Musselmann K, Hassell JR. Focus on molecules: CHST6 (carbohydrate sulfotransferase 6; corneal N-acetylglucosamine-6-sulfotransferase). Exp Eye Res. 2006; 83:707–708.

13. Aldave AJ, Yellore VS, Thonar EJ, et al. Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy. Am J Ophthalmol. 2004; 137:465–473.

14. Liu NP, Dew-Knight S, Rayner M, et al. Mutations in corneal carbohydrate sulfotransferase 6 gene (CHST6) cause macular corneal dystrophy in Iceland. Mol Vis. 2000; 6:261–264.

15. Warren JF, Aldave AJ, Srinivasan M, et al. Novel mutations in the CHST6 gene associated with macular corneal dystrophy in southern India. Arch Ophthalmol. 2003; 121:1608–1612.