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John F. Warren, MD; Anthony J. Aldave, MD; M. Srinivasan, MD; Eugene J. Thonar, PhD; Abha B. Kumar, MD; Vicky Cevallos, BS; John P. Whitcher, MD, MPH; Todd P. Margolis, MD, PhD

Arch Ophthalmol. 2003;121:1608-1612.

Objective  To further characterize the role of the carbohydrate sulfotransferase (CHST6) gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from southern India.

Methods  Genomic DNA was extracted from buccal epithelium of 75 patients (51 families) with MCD, 33 unaffected relatives, and 48 healthy volunteers. The coding region of the CHST6 gene was evaluated by means of polymerase chain reaction amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate.

Results  Seventy patients were classified as having type I MCD, and 5 patients as having type II MCD. Analysis of the CHST6 coding region in patients with type I MCD identified 11 homozygous missense mutations (Leu22Arg, His42Tyr, Arg50Cys, Arg50Leu, Ser53Leu, Arg97Pro, Cys102Tyr, Arg127Cys, Arg205Gln, His249Pro, and Glu274Lys), 2 compound heterozygous missense mutations (Arg93His and Ala206Thr), 5 homozygous deletion mutations (delCG707-708, delC890, delA1237, del1748-1770, and delORF), and 2 homozygous replacement mutations (ACCTAC 1273 GGT, and GCG 1304 AT). One patient with type II MCD was heterozygous for the C890 deletion mutation, whereas 4 possessed no CHST6 coding region mutations.

Conclusion  A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I MCD in a cohort of patients in southern India.

Clinical Relevance  An improved understanding of the genetic basis of MCD allows for earlier, more accurate diagnosis of affected individuals, and may provide the foundation for the development of novel disease treatments.

From the Francis I. Proctor Foundation and the Department of Ophthalmology, University of California–San Francisco (Drs Warren, Aldave, Kumar, Whitcher, and Margolis and Ms Cevallos); the Cornea and External Disease Service, Aravind Eye Hospital, Madurai, India (Dr Srinivasan); and the Departments of Biochemistry, Orthopedic Surgery, and Internal Medicine, Rush Medical College, Chicago, Ill (Dr Thonar). Dr Aldave is now with the Jules Stein Eye Institute, University of California–Los Angeles. The authors have no relevant financial interest in this article.

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