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Macular corneal dystrophy: mutational spectrum in German patients, novel mutations and therapeutic options

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Abstract

Introduction

The objective of this study was to investigate genotype-phenotype correlations, the consequences for surgical treatment, and the therapeutical options in patients with macular corneal dystrophy (MCD).

Material and methods

We investigated MCD genotype by using polymerase chain reaction followed by direct sequencing in one family and four patients with MCD. Results were confirmed by restriction analysis. Clinical phenotypes, histopathological findings, and therapeutical proceedings of each patient were reported and compared with the molecular genetic results.

Results

Five mutations, four missense mutations, and one frameshift mutation, from which three were novel, and one single-nucleotide polymorphism, were identified within the coding region of the CHST6 gene. In three patients, two with a homozygous mutation within the start codon (Met1Leu) and one with a heterozygous mutation (Leu200Arg) and a polymorphism (Arg162Gly), with irregular corneal surface and recurrent erosions a phototherapeutic keratectomy lead to a transient success. An additional fitting of rigid gas permeable contact lenses in one patient could further improve irregular astigmatism. In two patients, one with a frameshift mutation (1734_1735delTG; Arg211Gln) and one with two compound heterozygous mutations (Leu200Arg; Leu173Phe) and an additional polymorphism (Arg162Gly) a penetrating keratoplasty improved BCVA without any recurrence of the opacities within the follow-up time.

Discussion

Different genotypes imply several phenotypes, which influence therapeutical proceedings in MCD patients. Our study shows the wide range of diagnostic findings and therapeutical options in patients suffering from macular corneal dystrophy depending on the genotype.

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References

  1. Jones ST, Zimmerman LE (1961) Histopathologic differentiation of granular, macular and lattice dystrophies of the cornea. Am J Ophthalmol 51:394–410

    PubMed  CAS  Google Scholar 

  2. Edward DP, Yue BY, Sugar J, Thonar EJ, SunderRaj N, Stock EL, Tso MO (1988) Heterogeneity in macular corneal dystrophy. Arch Ophthalmol 106:1579–1583

    PubMed  CAS  Google Scholar 

  3. Edward DP, Thonar EJ, Srinivasan M, Yue BJ, Tso MO (1990) Macular dystrophy of the cornea. A systemic disorder of keratan sulfate metabolism. Ophthalmology 97:1194–1200

    PubMed  CAS  Google Scholar 

  4. Klintworth GK, Oshima E, al-Rajhi A, al-Saif A, Thonar EJ, Karcioglu ZA (1997) Macular corneal dystrophy in Saudi Arabia: a study of 56 cases and recognition of a new immunophenotype. Am J Ophthalmol 124:9–18

    PubMed  CAS  Google Scholar 

  5. Akama TO, Nishida K, Nakayama J, Watanabe H, Ozaki K, Nakamura T, Dota A, Kawasaki S, Inoue Y, Maeda N, Yamamoto S, Fujiwara T, Thonar EJ, Shimomura Y, Kinoshita S, Tanigami A, Fukuda MN (2000) Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene. Nat Genet 26:237–241

    Article  PubMed  CAS  Google Scholar 

  6. El-Ashry MF, El-Aziz MM, Wilkins S, Cheetham ME, Wilkie SE, Hardcastle AJ, Halford S, Bayoumi AY, Ficker LA, Tuft S, Bhattacharya SS, Ebenezer ND (2002) Identification of novel mutations in the carbohydrate sulfotransferase gene (CHST6) causing macular corneal dystrophy. Invest Ophthalmol Vis Sci 43:377–382

    PubMed  Google Scholar 

  7. Niel F, Ellies P, Dighiero P, Soria J, Sabbagh C, San C, Renard G, Delpech M, Valleix S (2003) Truncating mutations in the carbohydrate sulfotransferase 6 gene (CHST6) result in macular corneal dystrophy. Invest Ophthalmol Vis Sci 44:2949–2953

    Article  PubMed  Google Scholar 

  8. Iida-Hasegawa N, Furuhata A, Hayatsu H, Murakami A, Fujiki K, Nakayasu K, Kanai A (2003) Mutations in the CHST6 gene in patients with macular corneal dystrophy: immunohistochemical evidence of heterogeneity. Invest Ophthalmol Vis Sci 44:3272–3277

    Article  PubMed  Google Scholar 

  9. Ha NT, Chau HM, Cung le X, Thanh TK, Fujiki K, Murakami A, Hiratsuka Y, Hasegawa N, Kanai A (2003) Identification of novel mutations of the CHST6 gene in Vietnamese families affected with macular corneal dystrophy in two generations. Cornea 22:508–511

    Article  PubMed  Google Scholar 

  10. Warren JF, Aldave AJ, Srinivasan M, Thonar EJ, Kumar AB, Cevallos V, Whitcher JP, Margolis TP (2003) Novel mutations in the CHST6 gene associated with macular corneal dystrophy in southern India. Arch Ophthalmol 121:1608–1612

    Article  PubMed  CAS  Google Scholar 

  11. Sultana A, Sridhar MS, Jagannathan A, Balasubramanian D, Kannabiran C, Klintworth GK (2003) Novel mutations of the carbohydrate sulfotransferase-6 (CHST6) gene causing macular corneal dystrophy in India. Mol Vis 9:730–734

    PubMed  CAS  Google Scholar 

  12. Abbruzzese C, Kuhn U, Molina F, Rama P, De Luca M (2004) Novel mutations in the CHST6 gene causing macular corneal dystrophy. Clin Genet 65:120–125

    Article  PubMed  CAS  Google Scholar 

  13. Aldave AJ, Yellore VS, Thonar EJ, Udar N, Warren JF, Yoon MK, Cohen EJ, Rapuano CJ, Laibson PR, Margolis TP, Small K (2004) Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy. Am J Ophthalmol 137:465–473

    Article  PubMed  CAS  Google Scholar 

  14. El-Ashry MF, Abd El-Aziz MM, Shalaby O, Wilkins S, Poopalasundaram S, Cheetham M, Tuft SJ, Hardcastle AJ, Bhattacharya SS, Ebenezer ND (2005) Novel CHST6 nonsense and missense mutations responsible for macular corneal dystrophy. Am J Ophthalmol 139:192–193

    Article  PubMed  CAS  Google Scholar 

  15. Funderburgh JL, Caterson B, Conrad GW (1986) Keratan sulfate proteoglycan during embryonic development of the chicken cornea. Dev Biol 116:267–277

    Article  PubMed  CAS  Google Scholar 

  16. Cornet PK, Blochberger TC, Hassel JR (1994) Molecular polymorphism of lumican during corneal development. Invest Ophthalmol Vis Sci 35:870–877

    Google Scholar 

  17. Scott JE (1992) Morphometry of cupromeronic blue-stained proteoglycan molecules in animal corneas, versus that of purified proteoglycans stained in vitro, implies that tertiary structures contribute to corneal ultrastructure. J Anat 180:155–164

    PubMed  CAS  Google Scholar 

  18. Al-Swailem SA, Al-Rajhi AA, Wagoner MD (2005) Penetrating keratoplasty for macular corneal dystrophy. Ophthalmology 112:220–224

    Article  PubMed  Google Scholar 

  19. Hafner A, Langenbucher A, Seitz B (2005) Long-term results of phototherapeutic keratectomy with 193-nm excimer laser for macular corneal dystrophy. Am J Ophthalmol 140:392–396

    PubMed  Google Scholar 

  20. Fagerholm P (2003) Phototherapeutic keratectomy: 12 years of experience. Acta Ophthalmol Scand 81:19–32

    Article  PubMed  Google Scholar 

  21. Kuechle M, Cursiefen C, Fischer DC, Schlotzer-Schrehardt U, Naumann GO (1999) Recurrent macular corneal dystrophy type II 49 years after penetrating keratoplasty. Arch Ophthalmol 117:528–531

    Google Scholar 

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Acknowledgments

This study was supported by the European Social Fund and the State of Sachsen-Anhalt, Germany.

The authors thank Mrs. Katherine Dege, Germany, for her support of this study.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Martin Luther University Halle, Ernst-Grube-Str. 40, 06097, Halle, Germany

    Claudia Gruenauer-Kloevekorn & Gernot I. W. Duncker

  2. Department of Human Genetics, University of Leipzig, Philipp-Rosenthal-Str. 44, 04125, Leipzig, Germany

    Saskia Braeutigam, Wolfram Heinritz & Ursula G. Froster

Authors
  1. Claudia Gruenauer-Kloevekorn
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  2. Saskia Braeutigam
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  3. Wolfram Heinritz
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  4. Ursula G. Froster
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  5. Gernot I. W. Duncker
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Corresponding author

Correspondence to Claudia Gruenauer-Kloevekorn.

Additional information

This study was supported by the European Social Fond and the State of Sachsen-Anhalt, Germany.

The authors thank Mrs. Katherine Dege, Germany, for her approval of the manuscript.

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Gruenauer-Kloevekorn, C., Braeutigam, S., Heinritz, W. et al. Macular corneal dystrophy: mutational spectrum in German patients, novel mutations and therapeutic options. Graefes Arch Clin Exp Ophthalmol 246, 1441–1447 (2008). https://doi.org/10.1007/s00417-008-0836-1

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  • DOI: https://doi.org/10.1007/s00417-008-0836-1

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