CHST6 mutations identified in Iranian MCD patients and CHST6 mutations reported worldwide identify targets for gene edit
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ORIGINAL PAPER
CHST6 mutations identified in Iranian MCD patients and CHST6 mutations reported worldwide identify targets for gene editing approaches including the CRISPR/Cas system Iman Safari . Alireza Baradaran-Rafii . Shohreh Issazadeh-Navikas . Elahe Elahi
Received: 19 December 2019 / Accepted: 25 April 2020 Ó Springer Nature B.V. 2020
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.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10792-020-01401-9) contains supplementary material, which is available to authorized users. I. Safari E. Elahi (&) School of Biology, University College of Science, University of Tehran, Enghelab Ave, Tehran 1417614411, Iran e-mail: [email protected]; [email protected] A. Baradaran-Rafii Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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. Keywords Macular corneal dystrophy CHST6 MCD Mutation screening Potential mutation clusters
S. Issazadeh-Navikas Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark
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Int Ophthalmol
Introduction Macular corneal dystrophy (MCD; OMIM #217800) is a rare and severe form of corneal dystrophy that usually develops in childhood or adolescence [1–3]. It is a genetic disorder with an a
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