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M. F. Elashry, M. M. Abd El-Aziz, O. Shalaby, S. S. Bhattacharya; Mutation Screening of CHST6 Gene: Identification of Novel Mutations in Egyptian Patients With Macular Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1000.
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© ARVO (1962-2015); The Authors (2016-present)
To identify the underlying genetic defect in Egyptian patients with macular corneal dystrophy (MCD). Mutation screening of carbohydrate sulfotransferase gene (CHST6, OMIM 605294) was undertaken.
A clinical and genetic study was performed on one Egyptian family and 2 sporadic cases with MCD. The diagnosis was confirmed clinically by slit lamp examination and by further histopathological examination of corneal buttons after penetrating keratoplasty. The coding region of CHST6 was amplified by polymerase chain reaction (PCR). Sequence analysis of the purified PCR products was performed using an ABI 3730 automated sequencer. Nucleotide sequences were compared with the published cDNA sequence of CHST6 (GenBank accession number AF219990).
Three novel mutations were identified within the coding region of the CHST6 gene in three unrelated patients with MCD. All changes were homozygous, two were missense and the third was a two base pair deletion, c.606_607delCG, leading to a frameshift and premature stop codon. The first missense change is a T65C transition located at the second nucleotide position of codon 22, which changes the amino acid from leucine to proline. The second missense change, a C148A transversion located at the first nucleotide position of codon 50 leads to an arginine-to-serine substitution. None of these changes was detected in the control population of the same ethnic origin as investigated by sequence analysis of 100 control chromosomes, confirming that they are most likely to be pathogenic mutations.
This is the first report of CHST6 gene mutation screening in Egyptian population. The novel mutations detected occurred at positions in the protein structure where the residue type is highly conserved across carbohydrate sulfotransferases and/or involve non-conservative substitutions of charged to non- charged residues. These mutations within the coding region of CHST6 could result in loss of function of sulfotransferase enzyme required for proper sulfation of KS, an essential element for corneal transparency, leading to the MCD phenotype.
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