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MF El-Ashry, MM Abd El-Aziz, ND Ebenezer, S Wilkins, A Hardcasle, S Bhattacharya; Novel Mutations in CHST6 Gene Causing Macular Corneal Dystrophy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1655.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Macular corneal dystrophy (MCD) is an autosomal recessive disease characterized by progressive corneal opacities resulting in bilateral loss of vision. The disease has been classified into three immunophenotypes: MCD types I, IA, and II according to measurement of antigenic keratan sulfate (KS) in serum and immunohistochemical evaluation of corneal tissue. Recently, mutations in a carbohydrate sulfotranseferase gene (CHST6) were identified as the cause of MCD. Our aim was to identify the underlying mutations in two British families with MCD. Methods: Two unrelated British families with clinically and histopathologically diagnosed MCD participated in this study. 10 ml venous blood samples were taken from affected individuals, DNA was extracted and the coding region of CHST6 was amplified by the polymerase chain reaction (PCR). The amplified products were analysed by direct sequencing and restriction digest. Enzyme linked immunosorbent assay (ELISA) was performed on serum samples using anti KS antibody (5-D-4) to determine the immunophenotype of MCD. Results: Three novel heterozygous mutations were identified in the coding region of CHST6 gene. Two novel heterozygous mutations were found in a single family, the first is missense and located at the second nucleotide position of codon 276 (T/C) changing the amino acid from leucine to proline. The second change is non sense and located at the first nucleotide position of codon 140 (C/T) depicting change of the amino acid from arginine into a stop codon. The second family showed two heterozygous misense mutations, the first was reported recently by us and is located at the second nucleotide position of codon 200 (T/G) predicting the replacement of leucine by arginine. The second change is novel missense mutation and is located at the first nucleotide position of codon 357 (T/G) leading to substitution of tyrosine by aspartic acid. All mutations were excluded from at least 100 control chromosomes of the same ethnic origin by restriction enzyme analysis. ELISA showed that all our patients were of MCD type I. Conclusion: This study provides further evidence of the involvement of CHST6 gene in the pathogenesis of MCD.The wide spectrum of mutations identified in British population with MCD would make phenotype -genotype correlation feasible.
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