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CHST6 mutations identified in Iranian MCD patients and CHST6 mutations reported worldwide identify targets for gene editing approaches including the CRISPR/Cas system

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Abstract

Purpose

To identify CHST6 mutations in Iranians macular corneal dystrophy (MCD) patients and also to assess distribution of amino acids in the encoded protein that are affected by CHST6 mutations reported hitherto in various populations in order to predict gene regions that may be appropriate targets for gene editing approaches including the CRISPR/Cas system. The analysis will also reveal biologically and functionally important regions of the protein.

Methods

Mutation screening of CHST6 by sequencing was performed on 21 Iranian MCD-affected probands. Previously reported MCD causing CHST6 mutations were identified by searches in NCBI.

Results

Nineteen CHST6 mutations were found among the 21 Iranian patients, most of which were missense mutations and six of which were novel. Totally, 189 mutations among 375 MCD patients have been found worldwide, and 134 of these are missense mutations. The distribution of 88 amino acids affected by missense mutations along the length of the encoded protein was not random, and four regions of possible mutation clustering were noted. 25% of patients harbored mutations in a DNA region consisting of only 36 nucleotides.

Conclusion

Similar to most populations, CHST6 mutations among Iranians are very heterogeneous as indicated by finding 19 different mutations among 21 MCD patients. Nevertheless, identification of four potential mutation clusters identifies regions that are most suitable for gene therapy targeting by the CRISPR/Cas approach. Additionally, the mutation clusters identify regions with potential structural and/or functional importance. Consistent with this, the amino acids in these regions are well conserved among various membrane-bound sulfotransferases.

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Acknowledgements

We acknowledge the Ophthalmic Research Center of Shahid Beheshti University of Medical Sciences and Iran National Science Foundation for funding this research.

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Authors and Affiliations

  1. School of Biology, University College of Science, University of Tehran, Enghelab Ave, Tehran, 1417614411, Iran

    Iman Safari & Elahe Elahi

  2. Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Alireza Baradaran-Rafii

  3. Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark

    Shohreh Issazadeh-Navikas

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  1. Iman Safari
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  2. Alireza Baradaran-Rafii
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  3. Shohreh Issazadeh-Navikas
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  4. Elahe Elahi
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Correspondence to Elahe Elahi.

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Safari, I., Baradaran-Rafii, A., Issazadeh-Navikas, S. et al. CHST6 mutations identified in Iranian MCD patients and CHST6 mutations reported worldwide identify targets for gene editing approaches including the CRISPR/Cas system. Int Ophthalmol 40, 2223–2235 (2020). https://doi.org/10.1007/s10792-020-01401-9

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