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JF Warren, AJ Aldave, EJ Thonar, TP Margolis, JP Whitcher, M Srinivasan; Novel Mutations in the CHST6 Gene Associated With Macular Corneal Dystrophy in Southern India . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2870.
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Purpose:To further characterize the role of carbohydrate sulphotransferase 6 (CHST6) in macular corneal dystrophy (MCD) through identification of causative mutations. Methods:Genomic DNA was extracted from buccal epithelium of 29 patients with MCD, as well as unaffected relatives and controls. The coding region of CHST6 was evaluated by PCR amplification and direct sequencing. Subtyping of patients into types I and II was performed by measuring serum levels of sulphated keratan sulphate. Results:28 patients were classified as having type I MCD (undetectable levels of serum sulphated keratan sulphate), and 1 as having type II MCD (low levels of serum sulphated keratan sulphate). All unaffected relatives and controls had normal levels of serum sulphated keratan sulphate. Analysis of the CHST6 coding region identified 7 homozygous missense mutations (Leu22Arg, His42Tyr, Arg50Leu, Ser53Leu, Cys102Tyr, Arg205Gln, and His249Pro), 3 homozygous frameshift mutations (nucleotide deletions C707/G708, C890, and A1237), 1 homozygous replacement mutation (ACCTAC 1273 GGT), and 1 homozygous large deletion (deletion of ORF). Two patients (same family) were found to have compound heterozygous missense mutations (Arg93His, and Ala206Thr). No mutations were identified in the patient with type II MCD. Conclusion:A variety of previously unreported mutations in the CHST6 gene are associated with MCD in southern India. There do not appear to be any «hot spots» for disease-causing mutation in the CHST6 gene. Coding region mutations result in complete gene inactivation (undetectable levels of serum sulphated keratan sulphate) without phenotypic variation.
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